{"success":true,"data":{"pressRelease":{"id":"72926","rtpr_id":"nBw9dNvYja","ticker":"MRK","exchange":"NYSE","all_tickers":["MRK"],"title":"FDA Approves KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph), each with Trodelvy® (sacituzumab govitecan-hziy) as First-Line Treatment of PD-L1+ (CPS ≥10) Advanced Triple-Negative Breast Cancer (TNBC)","author":"Business Wire","published_at":"2026-06-25T10:45:00.095Z","article_body":"FDA Approves KEYTRUDA(®) (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab\nand berahyaluronidase alfa-pmph), each with Trodelvy(® )(sacituzumab\ngovitecan-hziy) as First-Line Treatment of PD-L1+ (CPS ≥10) Advanced\nTriple-Negative Breast Cancer (TNBC)\n\nFirst approval of PD‑1 inhibitors in combination with a Trop-2-directed\nantibody-drug conjugate (ADC) in advanced TNBC, marking a potentially\npractice‑changing treatment option\n\nMerck (NYSE: MRK), known as MSD outside of the United States and Canada, today\nannounced the U.S. Food and Drug Administration (FDA) approved KEYTRUDA(®\n)(pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase\nalfa-pmph), each in combination with Trodelvy(® )(sacituzumab\ngovitecan-hziy), Gilead’s Trop-2-directed antibody-drug conjugate (ADC), for\nthe first-line treatment of adult patients with unresectable locally advanced\nor metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1\n(Combined Positive Score [CPS] ≥10) as determined by an FDA-authorized test.\nThese approvals represent the first PD-1 inhibitors plus Trop-2-directed ADC\nregimen in advanced TNBC.\n\nThese approvals are based on data from the Phase 3 KEYNOTE-D19/ASCENT-04 trial\ndemonstrating that KEYTRUDA plus Trodelvy reduced the risk of disease\nprogression or death by 35% (HR=0.65 [95% CI, 0.51-0.84]; p=0.0009) versus\nKEYTRUDA plus chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine and\ncarboplatin) for the first-line treatment of adult patients with PD-L1+ (CPS\n≥10) unresectable locally advanced or metastatic TNBC. KEYTRUDA plus\nTrodelvy resulted in a median progression-free survival (PFS) of 11.2 months\n[95% CI, 9.3-16.7] versus 7.8 months [95% CI, 7.3-9.3] with KEYTRUDA plus\nchemotherapy. The objective response rate (ORR) was higher with KEYTRUDA plus\nTrodelvy (61% [95% CI, 55-68]) than with KEYTRUDA plus chemotherapy (55% [95%\nCI, 48-62]), and complete responses occurred in 12% and 8% of patients,\nrespectively. The effectiveness of KEYTRUDA QLEX for its approved indications\nhas been established based upon evidence from the adequate and well-controlled\nstudies conducted with KEYTRUDA and additional data from MK‑3475A‑D77\ncomparing the pharmacokinetic, efficacy and safety profiles of KEYTRUDA QLEX\nand KEYTRUDA.\n\n“For people living with metastatic triple-negative breast cancer, the first\ntreatment choice can be pivotal, as many patients may not have the opportunity\nto receive subsequent therapies,” said Sara Tolaney, MD, MPH, Chief of the\nDivision of Breast Oncology at Dana-Farber Cancer Institute and a principal\ninvestigator of Merck’s KEYNOTE-D19 and Gilead’s ASCENT-04 study. “These\napprovals are heartening news for patients and the clinical community, and I\nbelieve offer practice-changing first-line treatment options.”\n\nKEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to\nberahyaluronidase alfa, hyaluronidase or to any of its excipients. KEYTRUDA\nand KEYTRUDA QLEX are associated with the following Warnings and Precautions:\nsevere and fatal immune-mediated adverse reactions in any or multiple organs,\nwhich can occur during or after treatment, including pneumonitis, colitis,\nhepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ\ntransplant rejection, other transplant (including corneal graft) rejection;\nsevere and life-threatening infusion or injection-related reactions; fatal and\nother serious complications in patients who receive allogeneic hematopoietic\nstem cell transplantation before or after beginning treatment; embryo-fetal\ntoxicity; and increased mortality in patients with multiple myeloma when\nKEYTRUDA or KEYTRUDA QLEX is added to a thalidomide analogue plus\ndexamethasone, which is not recommended outside of controlled trials.\nImmune-mediated adverse reactions listed here may not include all such\npossible severe or fatal reactions. For more information, see “Selected\nImportant Safety Information” below.\n\n“Patients with PD-L1+ unresectable locally advanced or metastatic TNBC have\nlimited treatment options in the first-line setting, as this aggressive\ndisease often advances quickly,” said Dr. Gursel Aktan, vice president,\nglobal clinical development, Merck Research Laboratories. “We now have new\nfirst-line treatment options that combine, for the first time, a PD-1\ninhibitor with a Trop-2-directed ADC, and significantly reduce disease\nprogression or death compared to KEYTRUDA plus chemotherapy. Today’s\napprovals of KEYTRUDA and KEYTRUDA QLEX each in combination with Trodelvy\nrepresent a meaningful milestone for those living with advanced TNBC.”\n\nPembrolizumab (KEYTRUDA(®)) in combination with sacituzumab govitecan-hziy\n(Trodelvy(®)) is recommended by the National Comprehensive Cancer Network(®)\n(NCCN(®)) Clinical Practice Guidelines in Oncology (NCCN Guidelines(®)) for\nBreast Cancer as a category 1( )preferred first-line treatment option for\ncertain patients with recurrent unresectable (local or regional) or stage IV\n(M1) triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS\n≥10).*\n\n“For appropriate patients with metastatic TNBC, a new first‑line treatment\noption offers optimism to a community with historically few choices,” said\nRicki Fairley, co‑founder and CEO of TOUCH, The Black Breast Cancer\nAlliance. “TNBC disproportionately affects younger women – many in the\nprime of their lives – and often leads to poorer outcomes. Because so many\npatients may never receive subsequent lines of therapy, the ability to start\nwith options like Trodelvy with or without KEYTRUDA or KEYTRUDA QLEX is\ncritical. We have sought additional alternatives to chemotherapy-containing\nregimens in the first-line metastatic setting since TNBC was classified as a\ndisease more than 20 years ago. As such, these approvals represent meaningful\nprogress for the families impacted by this disease.”\n\nThe median duration of exposure to KEYTRUDA was 8.5 months (range 1 day to\n26.8 months).\n\nFatal adverse reactions occurred in 3.2% of patients receiving KEYTRUDA in\ncombination with sacituzumab govitecan-hziy, including death due to unknown\ncause (0.9%), and completed suicide, neutropenic sepsis, sepsis, pneumonia and\npulmonary embolism (0.5% each).\n\nSerious adverse reactions occurred in 38% of patients receiving KEYTRUDA in\ncombination with sacituzumab govitecan-hziy. Serious adverse reactions in\n≥2% of patients were febrile neutropenia (7%), neutropenia (6%), diarrhea\n(5%), fatigue and pneumonia (2.3% each).\n\nPermanent discontinuation of KEYTRUDA due to an adverse reaction occurred in\n9% of patients. The adverse reactions which resulted in permanent\ndiscontinuation of KEYTRUDA most commonly (≥1%) were pneumonitis and rash\n(1.4% each).\n\nDosage interruptions of KEYTRUDA due to adverse reactions occurred in 67% of\npatients. Adverse reactions which required dosage interruption in ≥2% of\npatients included neutropenia (36%), diarrhea (7%), upper respiratory tract\ninfection (4.5%), anemia (4.1%), fatigue (4.1%), increased alanine\naminotransferase (ALT) (3.2%), cough (2.7%), leukopenia (2.7%), nausea (2.7%),\npyrexia (2.7%), rash (2.7%), vomiting (2.7%) and COVID-19 (2.3%).\n\nThe most common (≥25%) adverse reactions, including laboratory\nabnormalities, occurring in patients treated with KEYTRUDA in combination with\nsacituzumab govitecan-hziy were decreased neutrophil count and decreased\nhemoglobin (86% each), decreased leukocyte count (84%), diarrhea (72%), nausea\n(68%), decreased lymphocyte count (61%), fatigue (58%), alopecia (52%),\nincreased alkaline phosphatase and increased glucose (50% each), increased ALT\n(47%), constipation (41%), increased aspartate aminotransferase (40%), rash\n(37%), decreased potassium (35%), increased lactate dehydrogenase (34%),\nvomiting (29%), abdominal pain, headache, and increased eosinophils (26% each)\nand decreased albumin (25%).\n\n*According to the NCCN Guidelines (Version 4.2026\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nccn.org%2Fprofessionals%2Fphysician_gls%2Fpdf%2Fbreast.pdf&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=Version+4.2026&index=1&md5=28d7c10f5d597d36fff6a9b89c80f76f)\n), category 1 is based upon high-level evidence (≥1 randomized phase 3\ntrials or high-quality, robust meta-analyses), there is uniform NCCN consensus\n(≥85% support of the Panel) that the intervention is appropriate. Preferred\nintervention refers to interventions that are based on superior efficacy,\nsafety, and evidence; and, when appropriate, affordability. NCCN makes no\nwarranties of any kind whatsoever regarding their content, use or application\nand disclaims any responsibility for their application or use in any way.\n\nAbout KEYNOTE-D19/ASCENT-04\n\nKEYNOTE-D19/ASCENT-04 (ClinicalTrials.gov, NCT05382286\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05382286&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=NCT05382286&index=2&md5=e4efcd5d7a4ddd0849c4cfdbefecfc4c)\n) is a Phase 3 multicenter, open-label, randomized, active-controlled trial\nevaluating KEYTRUDA in combination with sacituzumab govitecan-hziy in patients\nwith unresectable locally advanced or metastatic TNBC, who had not been\npreviously treated with systemic therapy for advanced disease and whose tumors\nexpressed PD-L1 (CPS ≥10) according to the PD-L1 IHC 22C3 pharmDx assay. The\nprimary efficacy endpoint was progression-free survival (PFS) as assessed by\nblinded independent central review (BICR) according to Response Evaluation\nCriteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary efficacy\nendpoints included overall survival (OS) and objective response rate (ORR) as\nassessed by BICR using RECIST v1.1. Safety also was evaluated. The study\nenrolled 443 patients who were randomized 1:1 to receive either KEYTRUDA (200\nmg intravenously [IV] on Day 1 of each 21-day cycle) plus sacituzumab\ngovitecan-hziy (10 mg/kg IV on Days 1 and 8 of each 21-day cycle) (n=221) or\nKEYTRUDA (200 mg IV on Day 1 of each 21-day cycle) plus chemotherapy (n=222).\nThe chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or\nnab-paclitaxel.\n\nAssessment of tumor status was performed every 8 weeks for the first 18\nmonths, and every 12 weeks thereafter. Treatment beyond BICR-verified disease\nprogression per RECIST 1.1 was permitted if the patient was clinically stable\nand considered to be deriving clinical benefit by the investigator. Crossover\nto sacituzumab govitecan-hziy monotherapy was offered following disease\nprogression and study treatment discontinuation.\n\nAbout triple-negative breast cancer (TNBC)\n\nTriple-negative breast cancer is an aggressive type of breast cancer; it has\nthe highest risk of recurrence within the first five years after treatment and\nis associated with worse outcomes compared to other forms of breast cancer.\nApproximately 10-15% of patients with breast cancer are diagnosed with TNBC.\nWhile some breast cancers may test positive for estrogen receptors (ER),\nprogesterone receptors (PR) or overexpression of human epidermal growth factor\nreceptor 2 (HER2), TNBC tests negative for ER and PR, and does not overexpress\nHER2. Triple-negative breast cancer tends to be more common in people who are\nyounger than age 40, who are Black or who have certain gene mutations.\n\nAbout KEYTRUDA(®) (pembrolizumab) injection for intravenous use, 100 mg\n\nKEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by\nincreasing the ability of the body’s immune system to help detect and fight\ntumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the\ninteraction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating\nT lymphocytes which may affect both tumor cells and healthy cells.\n\nMerck has the industry’s largest immuno-oncology clinical research program.\nThere are currently more than 2,800 trials studying KEYTRUDA across a wide\nvariety of cancers and treatment settings. The KEYTRUDA clinical program seeks\nto understand the role of KEYTRUDA across cancers and the factors that may\npredict a patient's likelihood of benefitting from treatment with KEYTRUDA,\nincluding exploring several different biomarkers.\n\nAbout KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph)\ninjection for subcutaneous use, 165 mg + 2,000 units/mL\n\nKEYTRUDA QLEX is a fixed-combination drug product of pembrolizumab and\nberahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1)\nblocking antibody and berahyaluronidase alfa enhances dispersion and\npermeability to enable subcutaneous administration of pembrolizumab. KEYTRUDA\nQLEX is administered as a subcutaneous injection into the thigh or abdomen,\navoiding the 5 cm area around the navel, over one minute every three weeks\n(2.4 mL) or over two minutes every six weeks (4.8 mL). KEYTRUDA QLEX must be\nadministered by a healthcare provider.\n\nSelected Indications in the U.S. for KEYTRUDA(®) (pembrolizumab) and KEYTRUDA\nQLEX™ (pembrolizumab and berahyaluronidase alfa-pmph)\n\nTriple-Negative Breast Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with high-risk early-stage triple-negative breast cancer (TNBC) in\ncombination with chemotherapy as neoadjuvant treatment, and then each\ncontinued as a single agent as adjuvant treatment after surgery.\n\nKEYTRUDA and KEYTRUDA QLEX, each in combination with sacituzumab\ngovitecan-hziy, are indicated for the first-line treatment of adult patients\nwith unresectable locally advanced or metastatic TNBC whose tumors express\nPD-L1 (CPS ≥10) as determined by an FDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nchemotherapy, for the treatment of adult patients with locally recurrent\nunresectable or metastatic triple-negative breast cancer (TNBC) whose tumors\nexpress PD-L1 (CPS ≥10) as determined by an FDA-authorized test.\n\nSee additional selected indications for KEYTRUDA and KEYTRUDA QLEX in the U.S.\nafter the Selected Safety Information.\n\nSelected Safety Information for KEYTRUDA and KEYTRUDA QLEX\n\nContraindications\n\nKEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to\nberahyaluronidase alfa, hyaluronidase or to any of its excipients.\n\nSevere and Fatal Immune-Mediated Adverse Reactions\n\nKEYTRUDA and KEYTRUDA QLEX are monoclonal antibodies that belong to a class of\ndrugs that bind to either the programmed death receptor-1 (PD-1) or the\nprogrammed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby\nremoving inhibition of the immune response, potentially breaking peripheral\ntolerance and inducing immune-mediated adverse reactions. Immune-mediated\nadverse reactions, which may be severe or fatal, can occur in any organ system\nor tissue, can affect more than one body system simultaneously, and can occur\nat any time after starting treatment or after discontinuation of treatment.\nImportant immune-mediated adverse reactions listed here may not include all\npossible severe and fatal immune-mediated adverse reactions.\n\nMonitor patients closely for symptoms and signs that may be clinical\nmanifestations of underlying immune-mediated adverse reactions. Early\nidentification and management are essential to ensure safe use of\nanti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid\nfunction at baseline and periodically during treatment. For patients with TNBC\ntreated with KEYTRUDA or KEYTRUDA QLEX in the neoadjuvant setting, monitor\nblood cortisol at baseline, prior to surgery, and as clinically indicated. In\ncases of suspected immune-mediated adverse reactions, initiate appropriate\nworkup to exclude alternative etiologies, including infection. Institute\nmedical management promptly, including specialty consultation as appropriate.\n\nWithhold or permanently discontinue KEYTRUDA and KEYTRUDA QLEX depending on\nseverity of the immune-mediated adverse reaction. In general, if KEYTRUDA and\nKEYTRUDA QLEX require interruption or discontinuation, administer systemic\ncorticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until\nimprovement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate\ncorticosteroid taper and continue to taper over at least 1 month. Consider\nadministration of other systemic immunosuppressants in patients whose adverse\nreactions are not controlled with corticosteroid therapy.\n\nImmune-Mediated Pneumonitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated pneumonitis. The\nincidence is higher in patients who have received prior thoracic radiation.\nImmune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving\nKEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2\n(1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of\npatients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3%\n(36) and withholding in 0.9% (26) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence.\nPneumonitis resolved in 59% of the 94 patients. Immune-mediated pneumonitis\noccurred in 5% (13/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy, including fatal (0.4%), Grade 3 (2%), and Grade 2 (1.2%)\nadverse reactions.\n\nPneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who\nreceived KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including\nfatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients\nreceived high-dose corticosteroids for a median duration of 10 days (range: 1\nday to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26\n(4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted\nKEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.\n\nImmune-Mediated Colitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated colitis, which may\npresent with diarrhea. Cytomegalovirus infection/reactivation has been\nreported in patients with corticosteroid-refractory immune-mediated colitis.\nIn cases of corticosteroid-refractory colitis, consider repeating infectious\nworkup to exclude alternative etiologies.\n\nImmune-mediated colitis occurred in 1.7% (48/2799) of patients receiving\nKEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%)\nreactions. Systemic corticosteroids were required in 69% (33/48); additional\nimmunosuppressant therapy was required in 4.2% of patients. Colitis led to\npermanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5%\n(13) of patients. All patients who were withheld reinitiated KEYTRUDA after\nsymptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of\nthe 48 patients. Immune-mediated colitis occurred in 1.2% (3/251) of patients\nreceiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 3\n(0.8%) and Grade 2 (0.4%) adverse reactions.\n\nHepatotoxicity and Immune-Mediated Hepatitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated hepatitis.\nImmune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving\nKEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%)\nreactions. Systemic corticosteroids were required in 68% (13/19) of patients;\nadditional immunosuppressant therapy was required in 11% of patients.\nHepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and\nwithholding in 0.3% (9) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, none had recurrence.\nHepatitis resolved in 79% of the 19 patients. Immune-mediated hepatitis\noccurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy, including Grade 2 (0.4%) adverse reactions.\n\nKEYTRUDA With Axitinib or KEYTRUDA QLEX With Axitinib\n\nKEYTRUDA and KEYTRUDA QLEX, when either is used in combination with axitinib,\ncan cause hepatic toxicity. Monitor liver enzymes before initiation of and\nperiodically throughout treatment. Consider monitoring more frequently as\ncompared to when the drugs are administered as single agents. For elevated\nliver enzymes, interrupt KEYTRUDA and axitinib or KEYTRUDA QLEX and axitinib,\nand consider administering corticosteroids as needed.\n\nWith the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased\nalanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase\n(AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone.\nFifty-nine percent of the patients with increased ALT received systemic\ncorticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN)\n(Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients\nwho were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34)\nadministered as a single agent or with both (n=55), recurrence of ALT ≥3\ntimes ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving\naxitinib, and 24 patients receiving both. All patients with a recurrence of\nALT ≥3 ULN subsequently recovered from the event.\n\nImmune-Mediated Endocrinopathies\n\nAdrenal Insufficiency\n\nKEYTRUDA and KEYTRUDA QLEX can cause primary or secondary adrenal\ninsufficiency. For Grade 2 or higher, initiate symptomatic treatment,\nincluding hormone replacement as clinically indicated. Withhold KEYTRUDA and\nKEYTRUDA QLEX depending on severity. Adrenal insufficiency occurred in 0.8%\n(22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade\n3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required\nin 77% (17/22) of patients; of these, the majority remained on systemic\ncorticosteroids. Adrenal insufficiency led to permanent discontinuation of\nKEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients\nwho were withheld reinitiated KEYTRUDA after symptom improvement. Adrenal\ninsufficiency occurred in 2% (5/251) of patients receiving KEYTRUDA QLEX in\ncombination with chemotherapy, including Grade 3 (0.4%) and Grade 2 (0.8%)\nadverse reactions.\n\nHypophysitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated hypophysitis.\nHypophysitis can present with acute symptoms associated with mass effect such\nas headache, photophobia, or visual field defects. Hypophysitis can cause\nhypopituitarism. Initiate hormone replacement as indicated. Withhold or\npermanently discontinue KEYTRUDA and KEYTRUDA QLEX depending on severity.\n\nHypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA,\nincluding Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions.\nSystemic corticosteroids were required in 94% (16/17) of patients; of these,\nthe majority remained on systemic corticosteroids. Hypophysitis led to\npermanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7)\nof patients. All patients who were withheld reinitiated KEYTRUDA after symptom\nimprovement.\n\nThyroid Disorders\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated thyroid disorders.\nThyroiditis can present with or without endocrinopathy. Hypothyroidism can\nfollow hyperthyroidism. Initiate hormone replacement for hypothyroidism or\ninstitute medical management of hyperthyroidism as clinically indicated.\nWithhold or permanently discontinue KEYTRUDA and KEYTRUDA QLEX depending on\nseverity.\n\nThyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA,\nincluding Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in\n<0.1% (1) of patients.\n\nHyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA,\nincluding Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent\ndiscontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of\npatients. All patients who were withheld reinitiated KEYTRUDA after symptom\nimprovement. Hypothyroidism occurred in 8% (237/2799) of patients receiving\nKEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent\ndiscontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of\npatients. All patients who were withheld reinitiated KEYTRUDA after symptom\nimprovement. The majority of patients with hypothyroidism required long-term\nthyroid hormone replacement. The incidence of new or worsening hypothyroidism\nwas higher in 1185 patients with HNSCC, occurring in 16% of patients receiving\nKEYTRUDA as a single agent or in combination with platinum and FU, including\nGrade 3 (0.3%) hypothyroidism. The incidence of new or worsening\nhyperthyroidism was higher in 580 patients with resected NSCLC, occurring in\n11% of patients receiving KEYTRUDA as a single agent as adjuvant treatment,\nincluding Grade 3 (0.2%) hyperthyroidism. The incidence of new or worsening\nhypothyroidism was higher in 580 patients with resected NSCLC, occurring in\n22% of patients receiving KEYTRUDA as a single agent as adjuvant treatment\n(KEYNOTE-091), including Grade 3 (0.3%) hypothyroidism.\n\nThyroiditis occurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in\ncombination with chemotherapy, including Grade 2 (0.4%). Hyperthyroidism\noccurred in 8% (20/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy, including Grade 2 (3.2%). Hypothyroidism occurred in 14%\n(35/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy,\nincluding Grade 2 (11%).\n\nType 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis\n\nMonitor patients for hyperglycemia or other signs and symptoms of diabetes.\nInitiate treatment with insulin as clinically indicated. Withhold KEYTRUDA and\nKEYTRUDA QLEX depending on severity. Type 1 DM occurred in 0.2% (6/2799) of\npatients receiving KEYTRUDA. It led to permanent discontinuation in <0.1%\n(1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who\nwere withheld reinitiated KEYTRUDA after symptom improvement. Type 1 DM\noccurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy.\n\nImmune-Mediated Nephritis With Renal Dysfunction\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated nephritis.\n\nImmune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving\nKEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%)\nreactions. Systemic corticosteroids were required in 89% (8/9) of patients.\nNephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and\nwithholding in 0.1% (3) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, none had recurrence.\nNephritis resolved in 56% of the 9 patients.\n\nImmune-Mediated Dermatologic Adverse Reactions\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated rash or dermatitis.\nExfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with\neosinophilia and systemic symptoms, and toxic epidermal necrolysis, has\noccurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical\ncorticosteroids may be adequate to treat mild to moderate nonexfoliative\nrashes. Withhold or permanently discontinue KEYTRUDA and KEYTRUDA QLEX\ndepending on severity.\n\nImmune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of\npatients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%)\nreactions. Systemic corticosteroids were required in 40% (15/38) of patients.\nThese reactions led to permanent discontinuation in 0.1% (2) and withholding\nof KEYTRUDA in 0.6% (16) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence.\nThe reactions resolved in 79% of the 38 patients. Immune-mediated dermatologic\nadverse reactions occurred in 1.6% (4/251) of patients receiving KEYTRUDA QLEX\nin combination with chemotherapy, including Grade 4 (0.8%) and Grade 3 (0.8%)\nadverse reactions.\n\nOther Immune-Mediated Adverse Reactions\n\nThe following clinically significant immune-mediated adverse reactions\noccurred at an incidence of <1% (unless otherwise noted) in patients who\nreceived KEYTRUDA, KEYTRUDA QLEX, or were reported with the use of other\nanti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for\nsome of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis,\nvasculitis; Nervous System: Meningitis, encephalitis, myelitis and\ndemyelination, myasthenic syndrome/myasthenia gravis (including exacerbation),\nGuillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular:\nUveitis, iritis and other ocular inflammatory toxicities can occur. Some cases\ncan be associated with retinal detachment. Various grades of visual\nimpairment, including blindness, can occur. If uveitis occurs in combination\nwith other immune-mediated adverse reactions, consider a\nVogt-Koyanagi-Harada-like syndrome, as this may require treatment with\nsystemic steroids to reduce the risk of permanent vision loss;\nGastrointestinal: Pancreatitis, to include increases in serum amylase and\nlipase levels, gastritis (2.8%), duodenitis; Musculoskeletal and Connective\nTissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae,\nincluding renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine:\nHypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia,\nhemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome,\nhistiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis,\nimmune thrombocytopenic purpura, solid organ transplant rejection, other\ntransplant (including corneal graft) rejection; Other:\nMyocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap syndrome,\nreported as the co-occurrence of either two or all three adverse reactions.\n\nHypersensitivity and Infusion- or Administration-Related Reactions\n\nKEYTRUDA and KEYTRUDA QLEX can cause severe or life-threatening\nadministration-related reactions, including hypersensitivity and anaphylaxis.\nWith KEYTRUDA and KEYTRUDA QLEX, monitor for signs and symptoms of infusion-\nand administration-related systemic reactions including rigors, chills,\nwheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.\nInfusion-related reactions have been reported in 0.2% of 2799 patients\nreceiving KEYTRUDA. Interrupt or slow the rate of infusion for Grade 1 or\nGrade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and\npermanently discontinue KEYTRUDA. Hypersensitivity and administration related\nsystemic reactions occurred in 3.2% (8/251) of patients receiving KEYTRUDA\nQLEX in combination with platinum doublet chemotherapy, including Grade 2\n(2.8%). Interrupt injection (if not already fully administered) and resume if\nsymptoms resolve for mild or moderate systemic reactions. For severe or\nlife-threatening systemic reactions, stop injection and permanently\ndiscontinue KEYTRUDA QLEX.\n\nComplications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)\n\nFatal and other serious complications can occur in patients who receive\nallogeneic HSCT before or after anti–PD-1/PD-L1 treatments.\nTransplant-related complications include hyperacute graft-versus-host disease\n(GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced\nintensity conditioning, and steroid-requiring febrile syndrome (without an\nidentified infectious cause). These complications may occur despite\nintervening therapy between anti–PD-1/PD-L1 treatments and allogeneic HSCT.\nFollow patients closely for evidence of these complications and intervene\npromptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments\nprior to or after an allogeneic HSCT.\n\nIncreased Mortality in Patients With Multiple Myeloma\n\nIn trials in patients with multiple myeloma, the addition of KEYTRUDA or\nKEYTRUDA QLEX to a thalidomide analogue plus dexamethasone resulted in\nincreased mortality. Treatment of these patients with an anti–PD-1/PD-L1\ntreatment in this combination is not recommended outside of controlled trials.\n\nEmbryofetal Toxicity\n\nBased on their mechanism of action, KEYTRUDA and KEYTRUDA QLEX can each cause\nfetal harm when administered to a pregnant woman. Advise women of this\npotential risk. In females of reproductive potential, verify pregnancy status\nprior to initiating KEYTRUDA or KEYTRUDA QLEX and advise them to use effective\ncontraception during treatment and for 4 months after the last dose.\n\nAdverse Reactions\n\nIn study MK-3475A-D77, when KEYTRUDA QLEX was administered with chemotherapy\nin metastatic non–small cell lung cancer (NSCLC), serious adverse reactions\noccurred in 39% of patients. Serious adverse reactions in ≥1% of patients\nwho received KEYTRUDA QLEX were pneumonia (10%), thrombocytopenia (4%),\nfebrile neutropenia (4%), neutropenia (2.8%), musculoskeletal pain (2%),\npneumonitis (2%), diarrhea (1.6%), rash (1.2%), respiratory failure (1.2%),\nand anemia (1.2%). Fatal adverse reactions occurred in 10% of patients\nincluding pneumonia (3.2%), neutropenic sepsis (2%), death not otherwise\nspecified (1.6%), respiratory failure (1.2%), parotitis (0.4%), pneumonitis\n(0.4%), pneumothorax (0.4%), pulmonary embolism (0.4%), neutropenic colitis\n(0.4%), and seizure (0.4%). KEYTRUDA QLEX was permanently discontinued due to\nan adverse reaction in 16% of 251 patients. Adverse reactions which resulted\nin permanent discontinuation of KEYTRUDA QLEX in ≥2% of patients included\npneumonia and pneumonitis. Dosage interruptions of KEYTRUDA QLEX due to an\nadverse reaction occurred in 45% of patients. Adverse reactions which required\ndosage interruption in ≥2% of patients included neutropenia, anemia,\nthrombocytopenia, pneumonia, rash, and increased aspartate aminotransferase.\nThe most common adverse reactions (≥20%) were nausea (25%), fatigue (25%),\nand musculoskeletal pain (21%).\n\nIn KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of\n555 patients with advanced melanoma; adverse reactions leading to permanent\ndiscontinuation in more than one patient were colitis (1.4%), autoimmune\nhepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac\nfailure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were\nfatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).\n\nIn KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients\nwith stage III melanoma, KEYTRUDA was permanently discontinued due to adverse\nreactions in 14% of 509 patients; the most common (≥1%) were pneumonitis\n(1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred\nin 25% of patients receiving KEYTRUDA. The most common adverse reaction\n(≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was\nadministered as a single agent to patients with stage IIB or IIC melanoma,\nadverse reactions occurring in patients with stage IIB or IIC melanoma were\nsimilar to those occurring in 1011 patients with stage III melanoma from\nKEYNOTE-054.\n\nIn KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum\nchemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to\nadverse reactions in 20% of 405 patients. The most common adverse reactions\nresulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and\nacute kidney injury (2%). The most common adverse reactions (≥20%) with\nKEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%),\ndecreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea\n(21%), and pyrexia (20%).\n\nIn KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either\npaclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA\nwas discontinued due to adverse reactions in 15% of 101 patients. The most\nfrequent serious adverse reactions reported in at least 2% of patients were\nfebrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions\nobserved in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the\nexception that increased incidences of alopecia (47% vs 36%) and peripheral\nneuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm\ncompared to the placebo and chemotherapy arm in KEYNOTE-407.\n\nIn KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of\n636 patients with advanced NSCLC; the most common were pneumonitis (3%), death\ndue to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious\nadverse reactions reported in at least 2% of patients were pneumonia (7%),\npneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%).\nThe most common adverse reaction (≥20%) was fatigue (25%).\n\nIn KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions\nin 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis\n(1.8%). The most common adverse reactions (≥20%) were decreased appetite\n(25%), fatigue (25%), dyspnea (23%), and nausea (20%).\n\nIn KEYNOTE-671, adverse reactions occurring in patients with resectable NSCLC\nreceiving KEYTRUDA in combination with platinum-containing chemotherapy, given\nas neoadjuvant treatment and continued as single-agent adjuvant treatment,\nwere generally similar to those occurring in patients in other clinical trials\nacross tumor types receiving KEYTRUDA in combination with chemotherapy.\n\nThe most common adverse reactions (reported in ≥20%) in patients receiving\nKEYTRUDA in combination with chemotherapy or chemoradiotherapy were\nfatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash,\nvomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal\ninflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia,\nmyalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection,\nhypothyroidism, radiation skin injury, dysphagia, dry mouth, and\nmusculoskeletal pain.\n\nIn the neoadjuvant phase of KEYNOTE-671, when KEYTRUDA was administered in\ncombination with platinum-containing chemotherapy as neoadjuvant treatment,\nserious adverse reactions occurred in 34% of 396 patients. The most frequent\n(≥2%) serious adverse reactions were pneumonia (4.8%), venous\nthromboembolism (3.3%), and anemia (2%). Fatal adverse reactions occurred in\n1.3% of patients, including death due to unknown cause (0.8%), sepsis (0.3%),\nand immune-mediated lung disease (0.3%). Permanent discontinuation of any\nstudy drug due to an adverse reaction occurred in 18% of patients who received\nKEYTRUDA in combination with platinum-containing chemotherapy; the most\nfrequent adverse reactions (≥1%) that led to permanent discontinuation of\nany study drug were acute kidney injury (1.8%), interstitial lung disease\n(1.8%), anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%).\n\nOf the KEYTRUDA-treated patients who received neoadjuvant treatment, 6% of 396\npatients did not receive surgery due to adverse reactions. The most frequent\n(≥1%) adverse reaction that led to cancellation of surgery in the KEYTRUDA\narm was interstitial lung disease (1%).\n\nIn the adjuvant phase of KEYNOTE-671, when KEYTRUDA was administered as a\nsingle agent as adjuvant treatment, serious adverse reactions occurred in 14%\nof 290 patients. The most frequent serious adverse reaction was pneumonia\n(3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred. Permanent\ndiscontinuation of KEYTRUDA due to an adverse reaction occurred in 12% of\npatients who received KEYTRUDA as a single agent, given as adjuvant treatment;\nthe most frequent adverse reactions (≥1%) that led to permanent\ndiscontinuation of KEYTRUDA were diarrhea (1.7%), interstitial lung disease\n(1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain\n(1%).\n\nAdverse reactions observed in KEYNOTE-091 were generally similar to those\noccurring in other patients with NSCLC receiving KEYTRUDA as a single agent,\nwith the exception of hypothyroidism (22%), hyperthyroidism (11%), and\npneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.\n\nAdverse reactions observed in KEYNOTE-483 were generally similar to those\noccurring in other patients receiving KEYTRUDA in combination with pemetrexed\nand platinum chemotherapy.\n\nIn KEYNOTE-689, the most common adverse reactions (≥20%) in patients\nreceiving KEYTRUDA were stomatitis (48%), radiation skin injury (40%), weight\nloss (36%), fatigue (33%), dysphagia (29%), constipation (27%), hypothyroidism\n(26%), nausea (24%), rash (22%), dry mouth (22%), diarrhea (22%), and\nmusculoskeletal pain (22%).\n\nIn the neoadjuvant phase of KEYNOTE-689, of the 361 patients who received at\nleast one dose of single agent KEYTRUDA, 11% experienced serious adverse\nreactions. Serious adverse reactions that occurred in more than one patient\nwere pneumonia (1.4%), tumor hemorrhage (0.8%), dysphagia (0.6%),\nimmune-mediated hepatitis (0.6%), cellulitis (0.6%), and dyspnea (0.6%). Fatal\nadverse reactions occurred in 1.1% of patients, including respiratory failure,\nclostridium infection, septic shock, and myocardial infarction (one patient\neach). Permanent discontinuation of KEYTRUDA due to an adverse reaction\noccurred in 2.8% of patients who received KEYTRUDA as neoadjuvant treatment.\nThe most frequent adverse reaction which resulted in permanent discontinuation\nof neoadjuvant KEYTRUDA in more than one patient was arthralgia (0.6%).\n\nOf the 361 patients who received KEYTRUDA as neoadjuvant treatment, 11% did\nnot receive surgery. Surgical cancellation on the KEYTRUDA arm was due to\ndisease progression in 4%, patient decision in 3%, adverse reactions in 1.4%,\nphysician’s decision in 1.1%, unresectable tumor in 0.6%, loss of follow-up\nin 0.3%, and use of non-study anti-cancer therapy in 0.3%.\n\nOf the 323 KEYTRUDA-treated patients who received surgery following the\nneoadjuvant phase, 1.2% experienced delay of surgery (defined as on-study\nsurgery occurring ≥9 weeks after initiation of neoadjuvant KEYTRUDA) due to\nadverse reactions, and 2.8% did not receive adjuvant treatment due to adverse\nreactions.\n\nIn the adjuvant phase of KEYNOTE-689, of the 255 patients who received at\nleast one dose of KEYTRUDA, 38% experienced serious adverse reactions. The\nmost frequent serious adverse reactions reported in ≥1% of KEYTRUDA-treated\npatients were pneumonia (2.7%), pyrexia (2.4%), stomatitis (2.4%), acute\nkidney injury (2.0%), pneumonitis (1.6%), COVID-19 (1.2%), death not otherwise\nspecified (1.2%), diarrhea (1.2%), dysphagia (1.2%), gastrostomy tube site\ncomplication (1.2%), and immune-mediated hepatitis (1.2%). Fatal adverse\nreactions occurred in 5% of patients, including death not otherwise specified\n(1.2%), acute renal failure (0.4%), hypercalcemia (0.4%), pulmonary hemorrhage\n(0.4%), dysphagia/malnutrition (0.4%), mesenteric thrombosis (0.4%), sepsis\n(0.4%), pneumonia (0.4%), COVID-19 (0.4%), respiratory failure (0.4%),\ncardiovascular disorder (0.4%), and gastrointestinal hemorrhage (0.4%).\nPermanent discontinuation of adjuvant KEYTRUDA due to an adverse reaction\noccurred in 17% of patients. The most frequent (≥1%) adverse reactions that\nled to permanent discontinuation of adjuvant KEYTRUDA were pneumonitis,\ncolitis, immune-mediated hepatitis, and death not otherwise specified.\n\nIn KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in\n12% of 300 patients with HNSCC; the most common adverse reactions leading to\npermanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most\ncommon adverse reactions (≥20%) were fatigue (33%), constipation (20%), and\nrash (20%).\n\nIn KEYNOTE-048, when KEYTRUDA was administered in combination with platinum\n(cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due\nto adverse reactions in 16% of 276 patients with HNSCC. The most common\nadverse reactions resulting in permanent discontinuation of KEYTRUDA were\npneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common\nadverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation\n(37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased\nappetite (29%), stomatitis (26%), and cough (22%).\n\nIn KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of\n192 patients with HNSCC. Serious adverse reactions occurred in 45% of\npatients. The most frequent serious adverse reactions reported in at least 2%\nof patients were pneumonia, dyspnea, confusional state, vomiting, pleural\neffusion, and respiratory failure. The most common adverse reactions (≥20%)\nwere fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in\npatients with HNSCC were generally similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception\nof increased incidences of facial edema and new or worsening hypothyroidism.\n\nIn KEYNOTE-A39, when KEYTRUDA was administered in combination with enfortumab\nvedotin to patients with locally advanced or metastatic urothelial cancer\n(n=440), fatal adverse reactions occurred in 3.9% of patients, including acute\nrespiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).\nSerious adverse reactions occurred in 50% of patients receiving KEYTRUDA in\ncombination with enfortumab vedotin; the serious adverse reactions in ≥2% of\npatients were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%),\nurinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia\n(2%), and hyperglycemia (2%). Permanent discontinuation of KEYTRUDA occurred\nin 27% of patients. The most common adverse reactions (≥2%) resulting in\npermanent discontinuation of KEYTRUDA were pneumonitis/ILD (4.8%) and rash\n(3.4%). The most common adverse reactions (≥20%) occurring in patients\ntreated with KEYTRUDA in combination with enfortumab vedotin were rash (68%),\nperipheral neuropathy (67%), fatigue (51%), pruritus (41%), diarrhea (38%),\nalopecia (35%), weight loss (33%), decreased appetite (33%), nausea (26%),\nconstipation (26%), dry eye (24%), dysgeusia (21%), and urinary tract\ninfection (21%).\n\nIn KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of\n370 patients with locally advanced or metastatic urothelial carcinoma. Serious\nadverse reactions occurred in 42% of patients; those ≥2% were urinary tract\ninfection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most\ncommon adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain\n(24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea\n(20%).\n\nIn KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of\n266 patients with locally advanced or metastatic urothelial carcinoma. The\nmost common adverse reaction resulting in permanent discontinuation of\nKEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of\nKEYTRUDA-treated patients; those ≥2% were urinary tract infection,\npneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%)\nin patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain\n(32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).\n\nIn KEYNOTE-905, the most common adverse reactions (≥20%) occurring in\ncisplatin-ineligible patients with MIBC treated with KEYTRUDA in combination\nwith enfortumab vedotin (n=167) were rash (54%), pruritus (47%), fatigue\n(47%), peripheral neuropathy (39%), alopecia (35%), dysgeusia (35%), diarrhea\n(34%), constipation (28%), decreased appetite (28%), nausea (26%), urinary\ntract infection (24%), dry eye (21%), and weight loss (20%).\n\nIn the neoadjuvant phase of KEYNOTE-905, serious adverse reactions occurred in\n27% (n=167) of patients; the most frequent (≥2%) were urinary tract\ninfection (3.6%) and hematuria (2.4%). Fatal adverse reactions occurred in\n1.2% of patients, including myasthenia gravis and toxic epidermal necrolysis\n(0.6% each). Additional fatal adverse reactions were reported in 2.7% of\npatients in the post-surgery phase before adjuvant treatment started,\nincluding sepsis and intestinal obstruction (1.4% each). Permanent\ndiscontinuation of KEYTRUDA due to an adverse reaction occurred in 15% of\npatients; the most frequent (>1%) were rash (2.4%, including generalized\nexfoliative dermatitis), increased alanine aminotransferase, increased\naspartate aminotransferase, diarrhea, dysgeusia, and toxic epidermal\nnecrolysis (1.2% each). Of the 167 patients in the KEYTRUDA in combination\nwith enfortumab vedotin arm who received neoadjuvant treatment, 7 (4.2%)\npatients did not receive surgery due to adverse reactions. The adverse\nreactions that led to cancellation of surgery were acute myocardial\ninfarction, bile duct cancer, colon cancer, respiratory distress, urinary\ntract infection, and two deaths due to myasthenia gravis and toxic epidermal\nnecrolysis (0.6% each).\n\nOf the 146 patients who received neoadjuvant treatment with KEYTRUDA in\ncombination with enfortumab vedotin and underwent radical cystectomy, 6 (4.1%)\npatients experienced delay of surgery (defined as time from last neoadjuvant\ntreatment to surgery exceeding 8 weeks) due to adverse reactions.\n\nIn the adjuvant phase of KEYNOTE-905, serious adverse reactions occurred in\n43% (n=100) of patients; the most frequent (≥2%) were urinary tract\ninfection (8%); acute kidney injury and pyelonephritis (5% each); urosepsis\n(4%); and hypokalemia, intestinal obstruction, and sepsis (2% each). Fatal\nadverse reactions occurred in 7% of patients, including urosepsis,\nintracranial hemorrhage, death, myocardial infarction, multiple organ\ndysfunction syndrome, and pseudomonal pneumonia (1% each). Permanent\ndiscontinuation of KEYTRUDA due to an adverse reaction occurred in 28% of\npatients; the most frequent (>1%) were diarrhea (5%), peripheral\nneuropathy, acute kidney injury, and pneumonitis (2% each).\n\nIn KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of\n148 patients with high-risk NMIBC. The most common adverse reaction resulting\nin permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious\nadverse reactions occurred in 28% of patients; those ≥2% were pneumonia\n(3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis\n(2%), and urinary tract infection (2%). The most common adverse reactions\n(≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).\n\nAdverse reactions occurring in patients with MSI-H or dMMR CRC were similar to\nthose occurring in patients with melanoma or NSCLC who received KEYTRUDA as a\nmonotherapy.\n\nIn KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with\nMSI-H or dMMR cancer were similar to those occurring in patients with other\nsolid tumors who received KEYTRUDA as a single agent.\n\nIn KEYNOTE-811, fatal adverse reactions occurred in 3 patients who received\nKEYTRUDA in combination with trastuzumab and CAPOX (capecitabine plus\noxaliplatin) or FP (5-FU plus cisplatin) and included pneumonitis in 2\npatients and hepatitis in 1 patient. KEYTRUDA was discontinued due to adverse\nreactions in 13% of 350 patients with locally advanced unresectable or\nmetastatic HER2-positive gastric or GEJ adenocarcinoma. Adverse reactions\nresulting in permanent discontinuation of KEYTRUDA in ≥1% of patients were\npneumonitis (2.0%) and pneumonia (1.1%). In the KEYTRUDA arm vs placebo, there\nwas a difference of ≥5% incidence between patients treated with KEYTRUDA vs\nstandard of care for diarrhea (53% vs 47%), rash (35% vs 28%), hypothyroidism\n(11% vs 5%), and pneumonia (11% vs 5%).\n\nIn KEYNOTE-859, when KEYTRUDA was administered in combination with\nfluoropyrimidine- and platinum-containing chemotherapy, serious adverse\nreactions occurred in 45% of 785 patients. Serious adverse reactions in >2%\nof patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%), and\nvomiting (2.4%). Fatal adverse reactions occurred in 8% of patients who\nreceived KEYTRUDA, including infection (2.3%) and thromboembolism (1.3%).\nKEYTRUDA was permanently discontinued due to adverse reactions in 15% of\npatients. The most common adverse reactions resulting in permanent\ndiscontinuation of KEYTRUDA (≥1%) were infections (1.8%) and diarrhea\n(1.0%). The most common adverse reactions (reported in ≥20%) in patients\nreceiving KEYTRUDA in combination with chemotherapy were peripheral neuropathy\n(47%), nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased\nappetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia\nsyndrome (25%), constipation (22%), and weight loss (20%).\n\nIn KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil\nto patients with metastatic or locally advanced esophageal or GEJ (tumors with\nepicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates\nfor surgical resection or definitive chemoradiation, KEYTRUDA was discontinued\ndue to adverse reactions in 15% of 370 patients. The most common adverse\nreactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were\npneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most\ncommon adverse reactions (≥20%) with KEYTRUDA in combination with\nchemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%),\nconstipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and\nweight loss (24%).\n\nAdverse reactions occurring in patients with esophageal cancer who received\nKEYTRUDA as a monotherapy were similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a monotherapy.\n\nIn KEYNOTE-A18, when KEYTRUDA was administered with CRT (cisplatin plus\nexternal beam radiation therapy [EBRT] followed by brachytherapy [BT]) to\npatients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse reactions\noccurred in 1.4% of 294 patients, including 1 case each (0.3%) of large\nintestinal perforation, urosepsis, sepsis, and vaginal hemorrhage. Serious\nadverse reactions occurred in 34% of patients; those ≥1% included urinary\ntract infection (3.1%), urosepsis (1.4%), and sepsis (1%). KEYTRUDA was\ndiscontinued for adverse reactions in 9% of patients. The most common adverse\nreaction (≥1%) resulting in permanent discontinuation was diarrhea (1%). For\npatients treated with KEYTRUDA in combination with CRT, the most common\nadverse reactions (≥10%) were nausea (56%), diarrhea (51%), urinary tract\ninfection (35%), vomiting (34%), fatigue (28%), hypothyroidism (23%),\nconstipation (20%), weight loss (19%), decreased appetite (18%), pyrexia\n(14%), abdominal pain and hyperthyroidism (13% each), dysuria and rash (12%\neach), back and pelvic pain (11% each), and COVID-19 (10%).\n\nIn KEYNOTE-826, when KEYTRUDA was administered in combination with paclitaxel\nand cisplatin or paclitaxel and carboplatin, with or without bevacizumab\n(n=307), to patients with persistent, recurrent, or first-line metastatic\ncervical cancer regardless of tumor PD-L1 expression who had not been treated\nwith chemotherapy except when used concurrently as a radio-sensitizing agent,\nfatal adverse reactions occurred in 4.6% of patients, including 3 cases of\nhemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each\nof acute myocardial infarction, autoimmune encephalitis, cardiac arrest,\ncerebrovascular accident, femur fracture with perioperative pulmonary embolus,\nintestinal perforation, and pelvic infection. Serious adverse reactions\noccurred in 50% of patients receiving KEYTRUDA in combination with\nchemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia\n(6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury\nand sepsis (3.3% each).\n\nKEYTRUDA was discontinued in 15% of patients due to adverse reactions. The\nmost common adverse reaction resulting in permanent discontinuation (≥1%)\nwas colitis (1%).\n\nFor patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the\nmost common adverse reactions (≥20%) were peripheral neuropathy (62%),\nalopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia\n(41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each),\nconstipation and arthralgia (31% each), vomiting (30%), urinary tract\ninfection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and\ndecreased appetite (21%).\n\nFor patients treated with KEYTRUDA in combination with chemotherapy with or\nwithout bevacizumab, the most common adverse reactions (≥20%) were\nperipheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%),\ndiarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%),\nhypertension and urinary tract infection (24% each), and rash (22%).\n\nIn KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98\npatients with previously treated recurrent or metastatic cervical cancer.\nSerious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the\nmost frequent included anemia (7%), fistula, hemorrhage, and infections\n[except urinary tract infections] (4.1% each). The most common adverse\nreactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea\n(23%), pain and abdominal pain (22% each), and decreased appetite (21%).\n\nIn KEYNOTE-394, KEYTRUDA was discontinued due to adverse reactions in 13% of\n299 patients with previously treated hepatocellular carcinoma. The most common\nadverse reaction resulting in permanent discontinuation of KEYTRUDA was\nascites (2.3%). The most common adverse reactions in patients receiving\nKEYTRUDA (≥10%) were pyrexia (18%), rash (18%), diarrhea (16%), decreased\nappetite (15%), pruritus (12%), upper respiratory tract infection (11%), cough\n(11%), and hypothyroidism (10%).\n\nIn KEYNOTE-966, when KEYTRUDA was administered in combination with gemcitabine\nand cisplatin, KEYTRUDA was discontinued for adverse reactions in 15% of 529\npatients with locally advanced unresectable or metastatic biliary tract\ncancer. The most common adverse reaction resulting in permanent\ndiscontinuation of KEYTRUDA (≥1%) was pneumonitis (1.3%). Adverse reactions\nleading to the interruption of KEYTRUDA occurred in 55% of patients. The most\ncommon adverse reactions or laboratory abnormalities leading to interruption\nof KEYTRUDA (≥2%) were decreased neutrophil count (18%), decreased platelet\ncount (10%), anemia (6%), decreased white blood cell count (4%), pyrexia\n(3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased\nAST (2.5%), and biliary obstruction (2.3%).\n\nIn KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with\nMCC (n=105) were generally similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a single agent.\n\nIn KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib,\nfatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse\nreactions occurred in 40% of patients, the most frequent (≥1%) were\nhepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration\n(1%), and pneumonitis (1%). Permanent discontinuation due to an adverse\nreaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only\n(13%), and the combination (8%); the most common were hepatotoxicity (13%),\ndiarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular\naccident (1.2%). The most common adverse reactions (≥20%) were diarrhea\n(56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%),\nhypothyroidism (35%), decreased appetite (30%), palmar-plantar\nerythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%),\ndysphonia (25%), rash (25%), cough (21%), and constipation (21%).\n\nIn KEYNOTE-564, when KEYTRUDA was administered as a single agent for the\nadjuvant treatment of renal cell carcinoma, serious adverse reactions occurred\nin 20% of patients receiving KEYTRUDA; the serious adverse reactions (≥1%)\nwere acute kidney injury, adrenal insufficiency, pneumonia, colitis, and\ndiabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2%\nincluding 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse\nreactions occurred in 21% of 488 patients; the most common (≥1%) were\nincreased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most\ncommon adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue\n(40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).\n\nIn KEYNOTE-868, when KEYTRUDA was administered in combination with\nchemotherapy (paclitaxel and carboplatin) to patients with advanced or\nrecurrent endometrial carcinoma (n=382), serious adverse reactions occurred in\n35% of patients receiving KEYTRUDA in combination with chemotherapy, compared\nto 19% of patients receiving placebo in combination with chemotherapy (n=377).\nFatal adverse reactions occurred in 1.6% of patients receiving KEYTRUDA in\ncombination with chemotherapy, including COVID-19 (0.5%) and cardiac arrest\n(0.3%). KEYTRUDA was discontinued for an adverse reaction in 14% of patients.\nAdverse reactions occurring in patients treated with KEYTRUDA and chemotherapy\nwere generally similar to those observed with KEYTRUDA alone or chemotherapy\nalone, with the exception of rash (33% all Grades; 2.9% Grades 3-4).\n\nAdverse reactions occurring in patients with MSI-H or dMMR endometrial\ncarcinoma who received KEYTRUDA as a single agent were similar to those\noccurring in patients with melanoma or NSCLC who received KEYTRUDA as a single\nagent.\n\nAdverse reactions occurring in patients with recurrent or metastatic cSCC or\nlocally advanced cSCC were similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a monotherapy.\n\nIn KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy\n(carboplatin and paclitaxel followed by doxorubicin or epirubicin and\ncyclophosphamide) followed by surgery and continued adjuvant treatment with\nKEYTRUDA as a single agent (n=778) to patients with newly diagnosed,\npreviously untreated, high-risk early-stage TNBC, fatal adverse reactions\noccurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune\nencephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and\nsepsis in association with multiple organ dysfunction syndrome and myocardial\ninfarction. Serious adverse reactions occurred in 44% of patients receiving\nKEYTRUDA; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia\n(2.6%), and neutropenia (2.2%). KEYTRUDA was discontinued in 20% of patients\ndue to adverse reactions. The most common reactions (≥1%) resulting in\npermanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and\nrash (1%). The most common adverse reactions (≥20%) in patients receiving\nKEYTRUDA with chemotherapy followed by KEYTRUDA alone were fatigue (70%),\nnausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and\nperipheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache\n(30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%),\ndecreased appetite (23%), insomnia (21%), and myalgia (20%).\n\nIn KEYNOTE-D19, when KEYTRUDA was administered in combination with sacituzumab\ngovitecan-hziy to patients with unresectable locally advanced or metastatic\nTNBC who had not been previously treated with systemic therapy for advanced\ndisease and whose tumors express PD-L1 (n=221), fatal adverse reactions\noccurred in 3.2% of patients, including death due to unknown cause (0.9%),\ncompleted suicide, neutropenic sepsis, sepsis, pneumonia, and pulmonary\nembolism (0.5% each).\n\nSerious adverse reactions occurred in 38% of patients receiving KEYTRUDA in\ncombination with sacituzumab govitecan-hziy. Serious adverse reactions in\n≥2% of patients were febrile neutropenia (7%), neutropenia (6%), diarrhea\n(5%), fatigue and pneumonia (2.3% each).\n\nPermanent discontinuation of KEYTRUDA due to an adverse reaction occurred in\n9% of patients. The adverse reactions which resulted in permanent\ndiscontinuation of KEYTRUDA most commonly (≥1%) were pneumonitis and rash\n(1.4% each).\n\nAdverse reactions leading to the interruption of KEYTRUDA occurred in 44% of\npatients. The most common adverse reactions leading to interruption of\nKEYTRUDA in ≥2% were urinary tract infection (3.9%), adrenal insufficiency\n(2.6%), pyrexia (2.6%), pneumonitis (2.6%), upper respiratory tract infection\n(2.6%), neutropenia (2.1%), diarrhea (2.1%) and COVID-19 (2.1%).\n\nThe most common (≥25%) adverse reactions, including laboratory\nabnormalities, occurring in patients treated with KEYTRUDA in combination with\nsacituzumab govitecan-hziy were decreased neutrophil count and decreased\nhemoglobin (86% each), decreased leukocyte count (84%), diarrhea (72%), nausea\n(68%), decreased lymphocyte count (61%), fatigue (58%), alopecia (52%),\nincreased alkaline phosphatase and increased glucose (50% each), increased\nalanine aminotransferase (47%), constipation (41%), increased aspartate\naminotransferase (40%), rash (37%), decreased potassium (35%), increased\nlactate dehydrogenase (34%), vomiting (29%), abdominal pain, headache, and\nincreased eosinophils, (26% each), and decreased albumin (25%).\n\nIn KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel\nprotein-bound, or gemcitabine and carboplatin) were administered to patients\nwith locally recurrent unresectable or metastatic TNBC who had not been\npreviously treated with chemotherapy in the metastatic setting (n=596), fatal\nadverse reactions occurred in 2.5% of patients, including cardio-respiratory\narrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in\n30% of patients receiving KEYTRUDA in combination with chemotherapy; the\nserious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and\nthrombocytopenia (2%). KEYTRUDA was discontinued in 11% of patients due to\nadverse reactions. The most common reactions resulting in permanent\ndiscontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and\npneumonitis (1.2%). The most common adverse reactions (≥20%) in patients\nreceiving KEYTRUDA in combination with chemotherapy were fatigue (48%), nausea\n(44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash\n(26% each), cough (23%), decreased appetite (21%), and headache (20%).\n\nIn KEYNOTE-B96, when KEYTRUDA in combination with paclitaxel, with or without\nbevacizumab, was administered to patients with epithelial ovarian, fallopian\ntube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1),\nserious adverse reactions occurred in 54% of patients receiving KEYTRUDA and\npaclitaxel with or without bevacizumab. Serious adverse reactions in ≥2% of\npatients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal\ninsufficiency, hyponatremia (3% each), COVID-19, decreased neutrophil count,\npulmonary embolism (2.6% each), abdominal pain, anemia, colitis, diarrhea,\nfebrile neutropenia, pyrexia, and vomiting (2.1% each).\n\nFatal adverse reactions occurred in 3.9% of patients receiving KEYTRUDA and\npaclitaxel, with or without bevacizumab, including assisted suicide (0.9%),\ndeath, intestinal perforation, sepsis, COVID-19, cardio-respiratory arrest,\ncolitis, and embolic stroke (0.4% each).\n\nKEYTRUDA was permanently discontinued for adverse reactions in 16% of\npatients. The most common adverse reactions resulting in permanent\ndiscontinuation of KEYTRUDA (≥1%) were colitis and increased alanine\naminotransferase (1.3% each). Adverse reactions leading to the interruption of\nKEYTRUDA occurred in 44% of patients. The most common adverse reactions\nleading to interruption of KEYTRUDA in ≥2% were urinary tract infection\n(3.9%), adrenal insufficiency, pyrexia, pneumonitis, upper respiratory tract\ninfection (2.6% each), neutropenia, diarrhea, and COVID-19 (2.1% each).\n\nThe most common adverse reactions (≥20%) for patients treated with KEYTRUDA\nin combination with paclitaxel, with or without bevacizumab, were diarrhea\n(45%), fatigue (43%), nausea (41%), alopecia, peripheral neuropathy (38%\neach), epistaxis (31%), urinary tract infection (27%), constipation (25%),\nabdominal pain, decreased appetite, vomiting (24% each), hypothyroidism (21%),\ncough, hypertension, and rash (20% each).\n\nFor patients treated with KEYTRUDA in combination with paclitaxel and\nbevacizumab (N=169), decreased white blood cell count (27%), stomatitis (22%),\nand pyrexia (21%) were also reported as adverse reactions.\n\nLactation\n\nBecause of the potential for serious adverse reactions in breastfed children,\nadvise women not to breastfeed during treatment and for 4 months after the\nlast dose.\n\nPediatric Use\n\nIn KEYNOTE-051, 173 pediatric patients (65 pediatric patients aged 6 months to\nyounger than 12 years and 108 pediatric patients aged 12 years to 17 years)\nwere administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of\nexposure was 2.1 months (range: 1 day to 25 months).\n\nThe safety and effectiveness of KEYTRUDA QLEX for the treatment of pediatric\npatients 12 years and older who weigh greater than 40 kg have been established\nfor:\n\n\n * Stage IIB, IIC, or III melanoma following complete resection\n\n * Unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch\nrepair deficient (dMMR) solid tumors\n\n * Recurrent locally advanced or metastatic Merkel cell carcinoma\n\nUse of KEYTRUDA QLEX in pediatric patients for these indications is supported\nby evidence from adequate and well-controlled studies of KEYTRUDA in adults\nand additional pharmacokinetic and safety data for KEYTRUDA in pediatric\npatients 12 years and older. Pembrolizumab exposures in pediatric patients 12\nyears and older who weigh greater than 40 kg are predicted to be within range\nof those observed in adults at the same dosage.\n\nThe safety and effectiveness of KEYTRUDA as a single agent have been\nestablished in pediatric patients with melanoma (stage IIB, IIC, or III\nmelanoma following complete resection in pediatric patients 12 and older),\nMCC, MSI-H or dMMR cancer.\n\nUse of KEYTRUDA in pediatric patients for these indications is supported by\nevidence from adequate and well-controlled studies in adults with additional\npharmacokinetic and safety data in pediatric patients.\n\nThe safety and effectiveness of KEYTRUDA QLEX have not been established in\npediatric patients younger than 12 years of age for the treatment of melanoma,\nMCC, MSI-H or dMMR cancer.\n\nThe safety and effectiveness of KEYTRUDA and KEYTRUDA QLEX have not been\nestablished in pediatric patients for other approved indications shown.\n\nAdverse reactions that occurred at a ≥10% higher rate in pediatric patients\nwhen compared to adults were pyrexia (33%), leukopenia (30%), vomiting (29%),\nneutropenia (28%), headache (25%), abdominal pain (23%), thrombocytopenia\n(22%), Grade 3 anemia (17%), decreased lymphocyte count (13%), and decreased\nwhite blood cell count (11%).\n\nGeriatric Use\n\nOf the 564 patients with locally advanced or metastatic urothelial cancer\ntreated with KEYTRUDA in combination with enfortumab vedotin, 44% (n=247) were\n65-74 years and 26% (n=144) were 75 years or older. No overall differences in\neffectiveness were observed between patients 65 years of age or older and\nyounger patients. Patients 75 years of age or older treated with KEYTRUDA in\ncombination with enfortumab vedotin experienced a higher incidence of fatal\nadverse reactions than younger patients. The incidence of fatal adverse\nreactions was 4% in patients younger than 75 and 7% in patients 75 years or\nolder.\n\nOf the 167 patients with MIBC treated with KEYTRUDA in combination with\nenfortumab vedotin, 37% (n=61) were 65-74 years and 46% (n=77) were 75 years\nor older. Patients 75 years of age or older treated with KEYTRUDA in\ncombination with enfortumab vedotin experienced a higher incidence of fatal\nadverse reactions than younger patients. The incidence of fatal adverse\nreactions was 4% in patients younger than 75 and 12% in patients 75 years or\nolder.\n\nAdditional Selected Indications in the U.S. for KEYTRUDA and KEYTRUDA QLEX\n\nMelanoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with unresectable or metastatic melanoma.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the adjuvant treatment of\nadult and pediatric patients 12 years and older with stage IIB, IIC, or III\nmelanoma following complete resection.\n\nNon-Small Cell Lung Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with pemetrexed\nand platinum chemotherapy, for the first-line treatment of adult patients with\nmetastatic nonsquamous non–small cell lung cancer (NSCLC), with no EGFR or\nALK genomic tumor aberrations.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with carboplatin\nand either paclitaxel or paclitaxel protein-bound, for the first-line\ntreatment of adult patients with metastatic squamous NSCLC.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\nfirst-line treatment of adult patients with NSCLC expressing PD-L1 [tumor\nproportion score (TPS) ≥1%] as determined by an FDA-authorized test, with no\nEGFR or ALK genomic tumor aberrations, and is:\n\n\n * stage III where patients are not candidates for surgical resection or\ndefinitive chemoradiation, or\n\n * metastatic.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with metastatic NSCLC whose tumors express PD-L1\n(TPS ≥1%) as determined by an FDA-authorized test, with disease progression\non or after platinum-containing chemotherapy. Patients with EGFR or ALK\ngenomic tumor aberrations should have disease progression on FDA-authorized\ntherapy for these aberrations prior to receiving KEYTRUDA or KEYTRUDA QLEX.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with resectable (tumors ≥4 cm or node positive) NSCLC in\ncombination with platinum-containing chemotherapy as neoadjuvant treatment,\nand then continued as a single agent as adjuvant treatment after surgery.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated as adjuvant\ntreatment following resection and platinum-based chemotherapy for adult\npatients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.\n\nMalignant Pleural Mesothelioma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with pemetrexed\nand platinum chemotherapy, for the first-line treatment of adult patients with\nunresectable advanced or metastatic malignant pleural mesothelioma (MPM).\n\nHead and Neck Squamous Cell Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with resectable locally advanced head and neck squamous cell\ncarcinoma (HNSCC) whose tumors express PD-L1 [Combined Positive Score (CPS)\n≥1] as determined by an FDA-authorized test, as a single agent as\nneoadjuvant treatment, continued as adjuvant treatment in combination with\nradiotherapy (RT) with or without cisplatin and then as a single agent.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with platinum\nand fluorouracil (FU), for the first-line treatment of adult patients with\nmetastatic or with unresectable, recurrent head and neck squamous cell\ncarcinoma (HNSCC).\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\nfirst-line treatment of adult patients with metastatic or with unresectable,\nrecurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by an\nFDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with recurrent or metastatic head and neck\nsquamous cell carcinoma (HNSCC) with disease progression on or after\nplatinum-containing chemotherapy.\n\nUrothelial Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with enfortumab\nvedotin, for the treatment of adult patients with locally advanced or\nmetastatic urothelial cancer.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with locally advanced or metastatic urothelial\ncarcinoma:\n\n\n * who are not eligible for any platinum-containing chemotherapy, or\n\n * who have disease progression during or following platinum-containing\nchemotherapy or within 12 months of neoadjuvant or adjuvant treatment with\nplatinum-containing chemotherapy.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with enfortumab\nvedotin, as neoadjuvant treatment and then continued after cystectomy as\nadjuvant treatment for the treatment of adult patients with muscle invasive\nbladder cancer (MIBC) who are ineligible for cisplatin-containing\nchemotherapy.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with Bacillus Calmette-Guerin (BCG)-unresponsive,\nhigh-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ\n(CIS) with or without papillary tumors who are ineligible for or have elected\nnot to undergo cystectomy.\n\nMicrosatellite Instability-High or Mismatch Repair Deficient Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with unresectable or metastatic microsatellite instability-high\n(MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an\nFDA-authorized test, that have progressed following prior treatment and who\nhave no satisfactory alternative treatment options. For this indication,\nKEYTRUDA also is indicated for the treatment of pediatric patients, and\nKEYTRUDA QLEX also is indicated for the treatment of pediatric patients 12\nyears and older.\n\nMicrosatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC)\nas determined by an FDA-authorized.\n\nGastric Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\ntrastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the\nfirst-line treatment of adults with locally advanced unresectable or\nmetastatic HER2-positive gastric or gastroesophageal junction (GEJ)\nadenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an\nFDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nfluoropyrimidine- and platinum-containing chemotherapy, for the first-line\ntreatment of adults with locally advanced unresectable or metastatic\nHER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose\ntumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test.\n\nEsophageal Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with locally advanced or metastatic esophageal or gastroesophageal\njunction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ)\ncarcinoma that is not amenable to surgical resection or definitive\nchemoradiation either:\n\n\n * in combination with platinum- and fluoropyrimidine-based chemotherapy for\npatients with tumors that express PD-L1 (CPS ≥1), or\n\n * as a single agent after one or more prior lines of systemic therapy for\npatients with tumors of squamous cell histology that express PD-L1 (CPS ≥10)\nas determined by an FDA-authorized test.\n\nCervical Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nchemoradiotherapy (CRT), for the treatment of adult patients with locally\nadvanced cervical cancer involving the lower third of the vagina, with or\nwithout extension to pelvic sidewall, or hydronephrosis/non-functioning\nkidney, or spread to adjacent pelvic organs (FIGO 2014 Stage III-IVA).\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nchemotherapy, with or without bevacizumab, for the treatment of adult patients\nwith persistent, recurrent, or metastatic cervical cancer whose tumors express\nPD-L1 (CPS ≥1) as determined by an FDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with recurrent or metastatic cervical cancer with\ndisease progression on or after chemotherapy whose tumors express PD-L1 (CPS\n≥1) as determined by an FDA-authorized test.\n\nHepatocellular Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have\nreceived prior systemic therapy other than a PD-1/PD-L1–containing regimen.\n\nBiliary Tract Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with gemcitabine\nand cisplatin, for the treatment of adult patients with locally advanced\nunresectable or metastatic biliary tract cancer (BTC).\n\nMerkel Cell Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with recurrent locally advanced or metastatic Merkel cell carcinoma\n(MCC). For this indication, KEYTRUDA also is indicated for the treatment of\npediatric patients, and KEYTRUDA QLEX also is indicated for the treatment of\npediatric patients 12 years and older.\n\nRenal Cell Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with axitinib,\nfor the first-line treatment of adult patients with advanced renal cell\ncarcinoma (RCC).\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the adjuvant treatment of\nadult patients with renal cell carcinoma (RCC) at intermediate high or high\nrisk of recurrence following nephrectomy, or following nephrectomy and\nresection of metastatic lesions.\n\nEndometrial Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with carboplatin\nand paclitaxel, followed by KEYTRUDA or KEYTRUDA QLEX as a single agent, for\nthe treatment of adult patients with primary advanced or recurrent endometrial\ncarcinoma.\n\nKEYTRUDA and KEYTRUDA QLEX, as a single agent, are each indicated for the\ntreatment of adult patients with advanced endometrial carcinoma that is MSI-H\nor dMMR, as determined by an FDA-authorized test, who have disease progression\nfollowing prior systemic therapy in any setting and are not candidates for\ncurative surgery or radiation.\n\nCutaneous Squamous Cell Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC)\nor locally advanced cSCC that is not curable by surgery or radiation.\n\nOvarian Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with paclitaxel,\nwith or without bevacizumab, for the treatment of adult patients with\nplatinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal\ncarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an\nFDA-authorized test, and who have received 1 or 2 prior systemic treatment\nregimens.\n\nAbout the Merck Access Program for KEYTRUDA and KEYTRUDA QLEX\n\nAt Merck, we are committed to supporting accessibility to our cancer\nmedicines. Merck provides multiple programs to help appropriate patients who\nare prescribed KEYTRUDA or KEYTRUDA QLEX have access to our anti-PD-1\ntherapies. The Merck Access Program provides reimbursement support for\npatients receiving KEYTRUDA and KEYTRUDA QLEX, including information to help\nwith out-of-pocket costs and co-pay assistance for eligible patients. More\ninformation is available by calling 855-257-3932 or visiting\nhttps://www.merckaccessprogram.com/\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merckaccessprogram.com%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merckaccessprogram.com%2F&index=3&md5=059c60549589d033b9240f26999048fe)\n.\n\nAbout Merck’s Patient Support Program for KEYTRUDA and KEYTRUDA QLEX\n\nMerck is committed to helping provide patients and their caregivers support\nthroughout their treatment with KEYTRUDA and KEYTRUDA QLEX. The My Merck\nSupport Program provides a range of resources and support. For further\ninformation and to sign up, eligible patients may call 888-55-MyMRK\n(888-556-9675) or visit https://www.mymercksupportteam.com/\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.mymercksupportteam.com%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.mymercksupportteam.com%2F&index=4&md5=abe90bdac879eb7e687d5b73322fb940)\n.\n\nMerck’s focus on cancer\n\nEvery day, we follow the science as we work to discover innovations that can\nhelp patients, no matter what stage of cancer they have. As a leading oncology\ncompany, we are pursuing research where scientific opportunity and medical\nneed converge, underpinned by our diverse pipeline of more than 20 novel\nmechanisms. With one of the largest clinical development programs across more\nthan 30 tumor types, we strive to advance breakthrough science that will shape\nthe future of oncology. By addressing barriers to clinical trial\nparticipation, screening and treatment, we work with urgency to reduce\ndisparities and help ensure patients have access to high-quality cancer care.\nOur unwavering commitment is what will bring us closer to our goal of bringing\nlife to more patients with cancer. For more information, visit\nwww.merck.com/research/oncology\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merck.com%2Fresearch%2Foncology%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=www.merck.com%2Fresearch%2Foncology&index=5&md5=74f28dc8203d173c2a76036ec0da13c6)\n.\n\nAbout Merck\n\nAt Merck, known as MSD outside of the United States and Canada, we are unified\naround our purpose: We use the power of leading-edge science to save and\nimprove lives around the world. For more than 130 years, we have brought hope\nto humanity through the development of important medicines and vaccines. We\naspire to be the premier research-intensive biopharmaceutical company in the\nworld – and today, we are at the forefront of research to deliver innovative\nhealth solutions that advance the prevention and treatment of diseases in\npeople and animals. We foster a diverse and inclusive global workforce and\noperate responsibly every day to enable a safe, sustainable and healthy future\nfor all people and communities. For more information, visit www.merck.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merck.com%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=www.merck.com&index=6&md5=a6c73ebbc30ae20ad211a6fd5401af97)\nand connect with us on X (formerly Twitter)\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fx.com%2FMerck&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=X+%28formerly+Twitter%29&index=7&md5=127b73bddc888fe11ea5055802293338)\n, Facebook\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.facebook.com%2FMerckInvents%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=Facebook&index=8&md5=f8bd48911e3ea0d59c059e574fff2930)\n, Instagram\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.instagram.com%2Fmerck%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=Instagram&index=9&md5=fb45d4d72b1c4ecbe7cd694fd530ecf1)\n, YouTube\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.youtube.com%2FMerck&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=YouTube&index=10&md5=986f3f8d8649ec56a62f1feb7aa4d8b2)\nand LinkedIn\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.linkedin.com%2Fcompany%2Fmerck&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=LinkedIn&index=11&md5=d95aef98a495c9ceb70781e085f3fa54)\n.\n\nForward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA\n\nThis news release of Merck & Co., Inc., Rahway, N.J., USA (the\n“company”) includes “forward-looking statements” within the meaning of\nthe safe harbor provisions of the U.S. Private Securities Litigation Reform\nAct of 1995. These statements are based upon the current beliefs and\nexpectations of the company’s management and are subject to significant\nrisks and uncertainties. There can be no guarantees with respect to pipeline\ncandidates that the candidates will receive the necessary regulatory approvals\nor that they will prove to be commercially successful. If underlying\nassumptions prove inaccurate or risks or uncertainties materialize, actual\nresults may differ materially from those set forth in the forward-looking\nstatements.\n\nRisks and uncertainties include but are not limited to, general industry\nconditions and competition; general economic factors, including interest rate\nand currency exchange rate fluctuations; the impact of pharmaceutical industry\nregulation and health care legislation in the United States and\ninternationally; global trends toward health care cost containment;\ntechnological advances, new products and patents attained by competitors;\nchallenges inherent in new product development, including obtaining regulatory\napproval; the company’s ability to accurately predict future market\nconditions; manufacturing difficulties or delays; financial instability of\ninternational economies and sovereign risk; dependence on the effectiveness of\nthe company’s patents and other protections for innovative products; and the\nexposure to litigation, including patent litigation, and/or regulatory\nactions.\n\nThe company undertakes no obligation to publicly update any forward-looking\nstatement, whether as a result of new information, future events or otherwise.\nAdditional factors that could cause results to differ materially from those\ndescribed in the forward-looking statements can be found in the company’s\nAnnual Report on Form 10-K for the year ended December 31, 2025 and the\ncompany’s other filings with the Securities and Exchange Commission (SEC)\navailable at the SEC’s Internet site (www.sec.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.sec.gov%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=www.sec.gov&index=12&md5=d2128632e9d9d305d7a933d2c2373576)\n).\n\nPlease see Prescribing Information for KEYTRUDA (pembrolizumab) at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fnam11.safelinks.protection.outlook.com%2F%3Furl%3Dhttps%253A%252F%252Fwww.merck.com%252Fproduct%252Fusa%252Fpi_circulars%252Fk%252Fkeytruda%252Fkeytruda_pi.pdf%26data%3D05%257C02%257Crmccarthy%2540realchemistry.com%257Ccc208a38b1524f6a5d0d08ded23aeec8%257C6fa5bfc4f95843f8bb395d382689654b%257C0%257C0%257C639179347744745628%257CUnknown%257CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%253D%253D%257C0%257C%257C%257C%26sdata%3DzjOHvlV1gS%252Fp5gWmwPZHgyFDhbGn58NqR6J2ohVfMgE%253D%26reserved%3D0&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda%2Fkeytruda_pi.pdf&index=13&md5=74e8fe4b4793ec499a3682247021daa8)\nand Medication Guide for KEYTRUDA at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda%2Fkeytruda_mg.pdf&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda%2Fkeytruda_mg.pdf&index=14&md5=5dca1a1969ace58179e1556e18150fbe)\n.\n\nPlease see Prescribing Information for KEYTRUDA QLEX™ (pembrolizumab and\nberahyaluronidase alfa-pmph) at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda_qlex/keytruda_qlex_pi.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fnam11.safelinks.protection.outlook.com%2F%3Furl%3Dhttps%253A%252F%252Fwww.merck.com%252Fproduct%252Fusa%252Fpi_circulars%252Fk%252Fkeytruda_qlex%252Fkeytruda_qlex_pi.pdf%26data%3D05%257C02%257Crmccarthy%2540realchemistry.com%257Ccc208a38b1524f6a5d0d08ded23aeec8%257C6fa5bfc4f95843f8bb395d382689654b%257C0%257C0%257C639179347744814207%257CUnknown%257CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%253D%253D%257C0%257C%257C%257C%26sdata%3DVxl2Q6NHtpc2J0yigwdC0utC42UEg2%252BMkYSyMoGTEGk%253D%26reserved%3D0&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda_qlex%2Fkeytruda_qlex_pi.pdf&index=15&md5=b537f1146b36e9308440e81a29791b8b)\nand Medication Guide for KEYTRUDA QLEX™ at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda_qlex/keytruda_qlex_mg.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fnam11.safelinks.protection.outlook.com%2F%3Furl%3Dhttps%253A%252F%252Fwww.merck.com%252Fproduct%252Fusa%252Fpi_circulars%252Fk%252Fkeytruda_qlex%252Fkeytruda_qlex_mg.pdf%26data%3D05%257C02%257Crmccarthy%2540realchemistry.com%257Ccc208a38b1524f6a5d0d08ded23aeec8%257C6fa5bfc4f95843f8bb395d382689654b%257C0%257C0%257C639179347744835582%257CUnknown%257CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%253D%253D%257C0%257C%257C%257C%26sdata%3DAa6luv5n7H%252FNLMU4UrON1MSRCWtWIUX%252BTQxJ6vybkgc%253D%26reserved%3D0&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda_qlex%2Fkeytruda_qlex_mg.pdf&index=16&md5=8b5d3b802f2a649565531475514e251d)\n.\n\n\n\nView source version on businesswire.com:\nhttps://www.businesswire.com/news/home/20260625926870/en/\n(https://www.businesswire.com/news/home/20260625926870/en/)\n\nMedia Contacts:\n\nJulie Cunningham\n\n(617) 519-6264\n\nDiane Foley\n\n(862) 260-0060\n\nInvestor Contacts:\n\nPeter Dannenbaum\n\n(732) 594-1579\n\nSteven Graziano\n\n(732) 594-1583\n\n\nCopyright Business Wire 2026","article_body_html":"","raw_payload":{"data":{"id":"nBw9dNvYja","title":"FDA Approves KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph), each with Trodelvy® (sacituzumab govitecan-hziy) as First-Line Treatment of PD-L1+ (CPS ≥10) Advanced Triple-Negative Breast Cancer (TNBC)","author":"Business Wire","ticker":"MRK","created":"2026-06-25T10:45:00.095Z","tickers":["MRK"],"exchange":"NYSE","article_body":"FDA Approves KEYTRUDA(®) (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab\nand berahyaluronidase alfa-pmph), each with Trodelvy(® )(sacituzumab\ngovitecan-hziy) as First-Line Treatment of PD-L1+ (CPS ≥10) Advanced\nTriple-Negative Breast Cancer (TNBC)\n\nFirst approval of PD‑1 inhibitors in combination with a Trop-2-directed\nantibody-drug conjugate (ADC) in advanced TNBC, marking a potentially\npractice‑changing treatment option\n\nMerck (NYSE: MRK), known as MSD outside of the United States and Canada, today\nannounced the U.S. Food and Drug Administration (FDA) approved KEYTRUDA(®\n)(pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase\nalfa-pmph), each in combination with Trodelvy(® )(sacituzumab\ngovitecan-hziy), Gilead’s Trop-2-directed antibody-drug conjugate (ADC), for\nthe first-line treatment of adult patients with unresectable locally advanced\nor metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1\n(Combined Positive Score [CPS] ≥10) as determined by an FDA-authorized test.\nThese approvals represent the first PD-1 inhibitors plus Trop-2-directed ADC\nregimen in advanced TNBC.\n\nThese approvals are based on data from the Phase 3 KEYNOTE-D19/ASCENT-04 trial\ndemonstrating that KEYTRUDA plus Trodelvy reduced the risk of disease\nprogression or death by 35% (HR=0.65 [95% CI, 0.51-0.84]; p=0.0009) versus\nKEYTRUDA plus chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine and\ncarboplatin) for the first-line treatment of adult patients with PD-L1+ (CPS\n≥10) unresectable locally advanced or metastatic TNBC. KEYTRUDA plus\nTrodelvy resulted in a median progression-free survival (PFS) of 11.2 months\n[95% CI, 9.3-16.7] versus 7.8 months [95% CI, 7.3-9.3] with KEYTRUDA plus\nchemotherapy. The objective response rate (ORR) was higher with KEYTRUDA plus\nTrodelvy (61% [95% CI, 55-68]) than with KEYTRUDA plus chemotherapy (55% [95%\nCI, 48-62]), and complete responses occurred in 12% and 8% of patients,\nrespectively. The effectiveness of KEYTRUDA QLEX for its approved indications\nhas been established based upon evidence from the adequate and well-controlled\nstudies conducted with KEYTRUDA and additional data from MK‑3475A‑D77\ncomparing the pharmacokinetic, efficacy and safety profiles of KEYTRUDA QLEX\nand KEYTRUDA.\n\n“For people living with metastatic triple-negative breast cancer, the first\ntreatment choice can be pivotal, as many patients may not have the opportunity\nto receive subsequent therapies,” said Sara Tolaney, MD, MPH, Chief of the\nDivision of Breast Oncology at Dana-Farber Cancer Institute and a principal\ninvestigator of Merck’s KEYNOTE-D19 and Gilead’s ASCENT-04 study. “These\napprovals are heartening news for patients and the clinical community, and I\nbelieve offer practice-changing first-line treatment options.”\n\nKEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to\nberahyaluronidase alfa, hyaluronidase or to any of its excipients. KEYTRUDA\nand KEYTRUDA QLEX are associated with the following Warnings and Precautions:\nsevere and fatal immune-mediated adverse reactions in any or multiple organs,\nwhich can occur during or after treatment, including pneumonitis, colitis,\nhepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ\ntransplant rejection, other transplant (including corneal graft) rejection;\nsevere and life-threatening infusion or injection-related reactions; fatal and\nother serious complications in patients who receive allogeneic hematopoietic\nstem cell transplantation before or after beginning treatment; embryo-fetal\ntoxicity; and increased mortality in patients with multiple myeloma when\nKEYTRUDA or KEYTRUDA QLEX is added to a thalidomide analogue plus\ndexamethasone, which is not recommended outside of controlled trials.\nImmune-mediated adverse reactions listed here may not include all such\npossible severe or fatal reactions. For more information, see “Selected\nImportant Safety Information” below.\n\n“Patients with PD-L1+ unresectable locally advanced or metastatic TNBC have\nlimited treatment options in the first-line setting, as this aggressive\ndisease often advances quickly,” said Dr. Gursel Aktan, vice president,\nglobal clinical development, Merck Research Laboratories. “We now have new\nfirst-line treatment options that combine, for the first time, a PD-1\ninhibitor with a Trop-2-directed ADC, and significantly reduce disease\nprogression or death compared to KEYTRUDA plus chemotherapy. Today’s\napprovals of KEYTRUDA and KEYTRUDA QLEX each in combination with Trodelvy\nrepresent a meaningful milestone for those living with advanced TNBC.”\n\nPembrolizumab (KEYTRUDA(®)) in combination with sacituzumab govitecan-hziy\n(Trodelvy(®)) is recommended by the National Comprehensive Cancer Network(®)\n(NCCN(®)) Clinical Practice Guidelines in Oncology (NCCN Guidelines(®)) for\nBreast Cancer as a category 1( )preferred first-line treatment option for\ncertain patients with recurrent unresectable (local or regional) or stage IV\n(M1) triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS\n≥10).*\n\n“For appropriate patients with metastatic TNBC, a new first‑line treatment\noption offers optimism to a community with historically few choices,” said\nRicki Fairley, co‑founder and CEO of TOUCH, The Black Breast Cancer\nAlliance. “TNBC disproportionately affects younger women – many in the\nprime of their lives – and often leads to poorer outcomes. Because so many\npatients may never receive subsequent lines of therapy, the ability to start\nwith options like Trodelvy with or without KEYTRUDA or KEYTRUDA QLEX is\ncritical. We have sought additional alternatives to chemotherapy-containing\nregimens in the first-line metastatic setting since TNBC was classified as a\ndisease more than 20 years ago. As such, these approvals represent meaningful\nprogress for the families impacted by this disease.”\n\nThe median duration of exposure to KEYTRUDA was 8.5 months (range 1 day to\n26.8 months).\n\nFatal adverse reactions occurred in 3.2% of patients receiving KEYTRUDA in\ncombination with sacituzumab govitecan-hziy, including death due to unknown\ncause (0.9%), and completed suicide, neutropenic sepsis, sepsis, pneumonia and\npulmonary embolism (0.5% each).\n\nSerious adverse reactions occurred in 38% of patients receiving KEYTRUDA in\ncombination with sacituzumab govitecan-hziy. Serious adverse reactions in\n≥2% of patients were febrile neutropenia (7%), neutropenia (6%), diarrhea\n(5%), fatigue and pneumonia (2.3% each).\n\nPermanent discontinuation of KEYTRUDA due to an adverse reaction occurred in\n9% of patients. The adverse reactions which resulted in permanent\ndiscontinuation of KEYTRUDA most commonly (≥1%) were pneumonitis and rash\n(1.4% each).\n\nDosage interruptions of KEYTRUDA due to adverse reactions occurred in 67% of\npatients. Adverse reactions which required dosage interruption in ≥2% of\npatients included neutropenia (36%), diarrhea (7%), upper respiratory tract\ninfection (4.5%), anemia (4.1%), fatigue (4.1%), increased alanine\naminotransferase (ALT) (3.2%), cough (2.7%), leukopenia (2.7%), nausea (2.7%),\npyrexia (2.7%), rash (2.7%), vomiting (2.7%) and COVID-19 (2.3%).\n\nThe most common (≥25%) adverse reactions, including laboratory\nabnormalities, occurring in patients treated with KEYTRUDA in combination with\nsacituzumab govitecan-hziy were decreased neutrophil count and decreased\nhemoglobin (86% each), decreased leukocyte count (84%), diarrhea (72%), nausea\n(68%), decreased lymphocyte count (61%), fatigue (58%), alopecia (52%),\nincreased alkaline phosphatase and increased glucose (50% each), increased ALT\n(47%), constipation (41%), increased aspartate aminotransferase (40%), rash\n(37%), decreased potassium (35%), increased lactate dehydrogenase (34%),\nvomiting (29%), abdominal pain, headache, and increased eosinophils (26% each)\nand decreased albumin (25%).\n\n*According to the NCCN Guidelines (Version 4.2026\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nccn.org%2Fprofessionals%2Fphysician_gls%2Fpdf%2Fbreast.pdf&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=Version+4.2026&index=1&md5=28d7c10f5d597d36fff6a9b89c80f76f)\n), category 1 is based upon high-level evidence (≥1 randomized phase 3\ntrials or high-quality, robust meta-analyses), there is uniform NCCN consensus\n(≥85% support of the Panel) that the intervention is appropriate. Preferred\nintervention refers to interventions that are based on superior efficacy,\nsafety, and evidence; and, when appropriate, affordability. NCCN makes no\nwarranties of any kind whatsoever regarding their content, use or application\nand disclaims any responsibility for their application or use in any way.\n\nAbout KEYNOTE-D19/ASCENT-04\n\nKEYNOTE-D19/ASCENT-04 (ClinicalTrials.gov, NCT05382286\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05382286&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=NCT05382286&index=2&md5=e4efcd5d7a4ddd0849c4cfdbefecfc4c)\n) is a Phase 3 multicenter, open-label, randomized, active-controlled trial\nevaluating KEYTRUDA in combination with sacituzumab govitecan-hziy in patients\nwith unresectable locally advanced or metastatic TNBC, who had not been\npreviously treated with systemic therapy for advanced disease and whose tumors\nexpressed PD-L1 (CPS ≥10) according to the PD-L1 IHC 22C3 pharmDx assay. The\nprimary efficacy endpoint was progression-free survival (PFS) as assessed by\nblinded independent central review (BICR) according to Response Evaluation\nCriteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary efficacy\nendpoints included overall survival (OS) and objective response rate (ORR) as\nassessed by BICR using RECIST v1.1. Safety also was evaluated. The study\nenrolled 443 patients who were randomized 1:1 to receive either KEYTRUDA (200\nmg intravenously [IV] on Day 1 of each 21-day cycle) plus sacituzumab\ngovitecan-hziy (10 mg/kg IV on Days 1 and 8 of each 21-day cycle) (n=221) or\nKEYTRUDA (200 mg IV on Day 1 of each 21-day cycle) plus chemotherapy (n=222).\nThe chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or\nnab-paclitaxel.\n\nAssessment of tumor status was performed every 8 weeks for the first 18\nmonths, and every 12 weeks thereafter. Treatment beyond BICR-verified disease\nprogression per RECIST 1.1 was permitted if the patient was clinically stable\nand considered to be deriving clinical benefit by the investigator. Crossover\nto sacituzumab govitecan-hziy monotherapy was offered following disease\nprogression and study treatment discontinuation.\n\nAbout triple-negative breast cancer (TNBC)\n\nTriple-negative breast cancer is an aggressive type of breast cancer; it has\nthe highest risk of recurrence within the first five years after treatment and\nis associated with worse outcomes compared to other forms of breast cancer.\nApproximately 10-15% of patients with breast cancer are diagnosed with TNBC.\nWhile some breast cancers may test positive for estrogen receptors (ER),\nprogesterone receptors (PR) or overexpression of human epidermal growth factor\nreceptor 2 (HER2), TNBC tests negative for ER and PR, and does not overexpress\nHER2. Triple-negative breast cancer tends to be more common in people who are\nyounger than age 40, who are Black or who have certain gene mutations.\n\nAbout KEYTRUDA(®) (pembrolizumab) injection for intravenous use, 100 mg\n\nKEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by\nincreasing the ability of the body’s immune system to help detect and fight\ntumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the\ninteraction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating\nT lymphocytes which may affect both tumor cells and healthy cells.\n\nMerck has the industry’s largest immuno-oncology clinical research program.\nThere are currently more than 2,800 trials studying KEYTRUDA across a wide\nvariety of cancers and treatment settings. The KEYTRUDA clinical program seeks\nto understand the role of KEYTRUDA across cancers and the factors that may\npredict a patient's likelihood of benefitting from treatment with KEYTRUDA,\nincluding exploring several different biomarkers.\n\nAbout KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph)\ninjection for subcutaneous use, 165 mg + 2,000 units/mL\n\nKEYTRUDA QLEX is a fixed-combination drug product of pembrolizumab and\nberahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1)\nblocking antibody and berahyaluronidase alfa enhances dispersion and\npermeability to enable subcutaneous administration of pembrolizumab. KEYTRUDA\nQLEX is administered as a subcutaneous injection into the thigh or abdomen,\navoiding the 5 cm area around the navel, over one minute every three weeks\n(2.4 mL) or over two minutes every six weeks (4.8 mL). KEYTRUDA QLEX must be\nadministered by a healthcare provider.\n\nSelected Indications in the U.S. for KEYTRUDA(®) (pembrolizumab) and KEYTRUDA\nQLEX™ (pembrolizumab and berahyaluronidase alfa-pmph)\n\nTriple-Negative Breast Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with high-risk early-stage triple-negative breast cancer (TNBC) in\ncombination with chemotherapy as neoadjuvant treatment, and then each\ncontinued as a single agent as adjuvant treatment after surgery.\n\nKEYTRUDA and KEYTRUDA QLEX, each in combination with sacituzumab\ngovitecan-hziy, are indicated for the first-line treatment of adult patients\nwith unresectable locally advanced or metastatic TNBC whose tumors express\nPD-L1 (CPS ≥10) as determined by an FDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nchemotherapy, for the treatment of adult patients with locally recurrent\nunresectable or metastatic triple-negative breast cancer (TNBC) whose tumors\nexpress PD-L1 (CPS ≥10) as determined by an FDA-authorized test.\n\nSee additional selected indications for KEYTRUDA and KEYTRUDA QLEX in the U.S.\nafter the Selected Safety Information.\n\nSelected Safety Information for KEYTRUDA and KEYTRUDA QLEX\n\nContraindications\n\nKEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to\nberahyaluronidase alfa, hyaluronidase or to any of its excipients.\n\nSevere and Fatal Immune-Mediated Adverse Reactions\n\nKEYTRUDA and KEYTRUDA QLEX are monoclonal antibodies that belong to a class of\ndrugs that bind to either the programmed death receptor-1 (PD-1) or the\nprogrammed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby\nremoving inhibition of the immune response, potentially breaking peripheral\ntolerance and inducing immune-mediated adverse reactions. Immune-mediated\nadverse reactions, which may be severe or fatal, can occur in any organ system\nor tissue, can affect more than one body system simultaneously, and can occur\nat any time after starting treatment or after discontinuation of treatment.\nImportant immune-mediated adverse reactions listed here may not include all\npossible severe and fatal immune-mediated adverse reactions.\n\nMonitor patients closely for symptoms and signs that may be clinical\nmanifestations of underlying immune-mediated adverse reactions. Early\nidentification and management are essential to ensure safe use of\nanti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid\nfunction at baseline and periodically during treatment. For patients with TNBC\ntreated with KEYTRUDA or KEYTRUDA QLEX in the neoadjuvant setting, monitor\nblood cortisol at baseline, prior to surgery, and as clinically indicated. In\ncases of suspected immune-mediated adverse reactions, initiate appropriate\nworkup to exclude alternative etiologies, including infection. Institute\nmedical management promptly, including specialty consultation as appropriate.\n\nWithhold or permanently discontinue KEYTRUDA and KEYTRUDA QLEX depending on\nseverity of the immune-mediated adverse reaction. In general, if KEYTRUDA and\nKEYTRUDA QLEX require interruption or discontinuation, administer systemic\ncorticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until\nimprovement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate\ncorticosteroid taper and continue to taper over at least 1 month. Consider\nadministration of other systemic immunosuppressants in patients whose adverse\nreactions are not controlled with corticosteroid therapy.\n\nImmune-Mediated Pneumonitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated pneumonitis. The\nincidence is higher in patients who have received prior thoracic radiation.\nImmune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving\nKEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2\n(1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of\npatients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3%\n(36) and withholding in 0.9% (26) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence.\nPneumonitis resolved in 59% of the 94 patients. Immune-mediated pneumonitis\noccurred in 5% (13/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy, including fatal (0.4%), Grade 3 (2%), and Grade 2 (1.2%)\nadverse reactions.\n\nPneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who\nreceived KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including\nfatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients\nreceived high-dose corticosteroids for a median duration of 10 days (range: 1\nday to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26\n(4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted\nKEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.\n\nImmune-Mediated Colitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated colitis, which may\npresent with diarrhea. Cytomegalovirus infection/reactivation has been\nreported in patients with corticosteroid-refractory immune-mediated colitis.\nIn cases of corticosteroid-refractory colitis, consider repeating infectious\nworkup to exclude alternative etiologies.\n\nImmune-mediated colitis occurred in 1.7% (48/2799) of patients receiving\nKEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%)\nreactions. Systemic corticosteroids were required in 69% (33/48); additional\nimmunosuppressant therapy was required in 4.2% of patients. Colitis led to\npermanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5%\n(13) of patients. All patients who were withheld reinitiated KEYTRUDA after\nsymptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of\nthe 48 patients. Immune-mediated colitis occurred in 1.2% (3/251) of patients\nreceiving KEYTRUDA QLEX in combination with chemotherapy, including Grade 3\n(0.8%) and Grade 2 (0.4%) adverse reactions.\n\nHepatotoxicity and Immune-Mediated Hepatitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated hepatitis.\nImmune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving\nKEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%)\nreactions. Systemic corticosteroids were required in 68% (13/19) of patients;\nadditional immunosuppressant therapy was required in 11% of patients.\nHepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and\nwithholding in 0.3% (9) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, none had recurrence.\nHepatitis resolved in 79% of the 19 patients. Immune-mediated hepatitis\noccurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy, including Grade 2 (0.4%) adverse reactions.\n\nKEYTRUDA With Axitinib or KEYTRUDA QLEX With Axitinib\n\nKEYTRUDA and KEYTRUDA QLEX, when either is used in combination with axitinib,\ncan cause hepatic toxicity. Monitor liver enzymes before initiation of and\nperiodically throughout treatment. Consider monitoring more frequently as\ncompared to when the drugs are administered as single agents. For elevated\nliver enzymes, interrupt KEYTRUDA and axitinib or KEYTRUDA QLEX and axitinib,\nand consider administering corticosteroids as needed.\n\nWith the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased\nalanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase\n(AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone.\nFifty-nine percent of the patients with increased ALT received systemic\ncorticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN)\n(Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients\nwho were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34)\nadministered as a single agent or with both (n=55), recurrence of ALT ≥3\ntimes ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving\naxitinib, and 24 patients receiving both. All patients with a recurrence of\nALT ≥3 ULN subsequently recovered from the event.\n\nImmune-Mediated Endocrinopathies\n\nAdrenal Insufficiency\n\nKEYTRUDA and KEYTRUDA QLEX can cause primary or secondary adrenal\ninsufficiency. For Grade 2 or higher, initiate symptomatic treatment,\nincluding hormone replacement as clinically indicated. Withhold KEYTRUDA and\nKEYTRUDA QLEX depending on severity. Adrenal insufficiency occurred in 0.8%\n(22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade\n3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required\nin 77% (17/22) of patients; of these, the majority remained on systemic\ncorticosteroids. Adrenal insufficiency led to permanent discontinuation of\nKEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients\nwho were withheld reinitiated KEYTRUDA after symptom improvement. Adrenal\ninsufficiency occurred in 2% (5/251) of patients receiving KEYTRUDA QLEX in\ncombination with chemotherapy, including Grade 3 (0.4%) and Grade 2 (0.8%)\nadverse reactions.\n\nHypophysitis\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated hypophysitis.\nHypophysitis can present with acute symptoms associated with mass effect such\nas headache, photophobia, or visual field defects. Hypophysitis can cause\nhypopituitarism. Initiate hormone replacement as indicated. Withhold or\npermanently discontinue KEYTRUDA and KEYTRUDA QLEX depending on severity.\n\nHypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA,\nincluding Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions.\nSystemic corticosteroids were required in 94% (16/17) of patients; of these,\nthe majority remained on systemic corticosteroids. Hypophysitis led to\npermanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7)\nof patients. All patients who were withheld reinitiated KEYTRUDA after symptom\nimprovement.\n\nThyroid Disorders\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated thyroid disorders.\nThyroiditis can present with or without endocrinopathy. Hypothyroidism can\nfollow hyperthyroidism. Initiate hormone replacement for hypothyroidism or\ninstitute medical management of hyperthyroidism as clinically indicated.\nWithhold or permanently discontinue KEYTRUDA and KEYTRUDA QLEX depending on\nseverity.\n\nThyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA,\nincluding Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in\n<0.1% (1) of patients.\n\nHyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA,\nincluding Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent\ndiscontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of\npatients. All patients who were withheld reinitiated KEYTRUDA after symptom\nimprovement. Hypothyroidism occurred in 8% (237/2799) of patients receiving\nKEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent\ndiscontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of\npatients. All patients who were withheld reinitiated KEYTRUDA after symptom\nimprovement. The majority of patients with hypothyroidism required long-term\nthyroid hormone replacement. The incidence of new or worsening hypothyroidism\nwas higher in 1185 patients with HNSCC, occurring in 16% of patients receiving\nKEYTRUDA as a single agent or in combination with platinum and FU, including\nGrade 3 (0.3%) hypothyroidism. The incidence of new or worsening\nhyperthyroidism was higher in 580 patients with resected NSCLC, occurring in\n11% of patients receiving KEYTRUDA as a single agent as adjuvant treatment,\nincluding Grade 3 (0.2%) hyperthyroidism. The incidence of new or worsening\nhypothyroidism was higher in 580 patients with resected NSCLC, occurring in\n22% of patients receiving KEYTRUDA as a single agent as adjuvant treatment\n(KEYNOTE-091), including Grade 3 (0.3%) hypothyroidism.\n\nThyroiditis occurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in\ncombination with chemotherapy, including Grade 2 (0.4%). Hyperthyroidism\noccurred in 8% (20/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy, including Grade 2 (3.2%). Hypothyroidism occurred in 14%\n(35/251) of patients receiving KEYTRUDA QLEX in combination with chemotherapy,\nincluding Grade 2 (11%).\n\nType 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis\n\nMonitor patients for hyperglycemia or other signs and symptoms of diabetes.\nInitiate treatment with insulin as clinically indicated. Withhold KEYTRUDA and\nKEYTRUDA QLEX depending on severity. Type 1 DM occurred in 0.2% (6/2799) of\npatients receiving KEYTRUDA. It led to permanent discontinuation in <0.1%\n(1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who\nwere withheld reinitiated KEYTRUDA after symptom improvement. Type 1 DM\noccurred in 0.4% (1/251) of patients receiving KEYTRUDA QLEX in combination\nwith chemotherapy.\n\nImmune-Mediated Nephritis With Renal Dysfunction\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated nephritis.\n\nImmune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving\nKEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%)\nreactions. Systemic corticosteroids were required in 89% (8/9) of patients.\nNephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and\nwithholding in 0.1% (3) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, none had recurrence.\nNephritis resolved in 56% of the 9 patients.\n\nImmune-Mediated Dermatologic Adverse Reactions\n\nKEYTRUDA and KEYTRUDA QLEX can cause immune-mediated rash or dermatitis.\nExfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with\neosinophilia and systemic symptoms, and toxic epidermal necrolysis, has\noccurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical\ncorticosteroids may be adequate to treat mild to moderate nonexfoliative\nrashes. Withhold or permanently discontinue KEYTRUDA and KEYTRUDA QLEX\ndepending on severity.\n\nImmune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of\npatients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%)\nreactions. Systemic corticosteroids were required in 40% (15/38) of patients.\nThese reactions led to permanent discontinuation in 0.1% (2) and withholding\nof KEYTRUDA in 0.6% (16) of patients. All patients who were withheld\nreinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence.\nThe reactions resolved in 79% of the 38 patients. Immune-mediated dermatologic\nadverse reactions occurred in 1.6% (4/251) of patients receiving KEYTRUDA QLEX\nin combination with chemotherapy, including Grade 4 (0.8%) and Grade 3 (0.8%)\nadverse reactions.\n\nOther Immune-Mediated Adverse Reactions\n\nThe following clinically significant immune-mediated adverse reactions\noccurred at an incidence of <1% (unless otherwise noted) in patients who\nreceived KEYTRUDA, KEYTRUDA QLEX, or were reported with the use of other\nanti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for\nsome of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis,\nvasculitis; Nervous System: Meningitis, encephalitis, myelitis and\ndemyelination, myasthenic syndrome/myasthenia gravis (including exacerbation),\nGuillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular:\nUveitis, iritis and other ocular inflammatory toxicities can occur. Some cases\ncan be associated with retinal detachment. Various grades of visual\nimpairment, including blindness, can occur. If uveitis occurs in combination\nwith other immune-mediated adverse reactions, consider a\nVogt-Koyanagi-Harada-like syndrome, as this may require treatment with\nsystemic steroids to reduce the risk of permanent vision loss;\nGastrointestinal: Pancreatitis, to include increases in serum amylase and\nlipase levels, gastritis (2.8%), duodenitis; Musculoskeletal and Connective\nTissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae,\nincluding renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine:\nHypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia,\nhemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome,\nhistiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis,\nimmune thrombocytopenic purpura, solid organ transplant rejection, other\ntransplant (including corneal graft) rejection; Other:\nMyocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap syndrome,\nreported as the co-occurrence of either two or all three adverse reactions.\n\nHypersensitivity and Infusion- or Administration-Related Reactions\n\nKEYTRUDA and KEYTRUDA QLEX can cause severe or life-threatening\nadministration-related reactions, including hypersensitivity and anaphylaxis.\nWith KEYTRUDA and KEYTRUDA QLEX, monitor for signs and symptoms of infusion-\nand administration-related systemic reactions including rigors, chills,\nwheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.\nInfusion-related reactions have been reported in 0.2% of 2799 patients\nreceiving KEYTRUDA. Interrupt or slow the rate of infusion for Grade 1 or\nGrade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and\npermanently discontinue KEYTRUDA. Hypersensitivity and administration related\nsystemic reactions occurred in 3.2% (8/251) of patients receiving KEYTRUDA\nQLEX in combination with platinum doublet chemotherapy, including Grade 2\n(2.8%). Interrupt injection (if not already fully administered) and resume if\nsymptoms resolve for mild or moderate systemic reactions. For severe or\nlife-threatening systemic reactions, stop injection and permanently\ndiscontinue KEYTRUDA QLEX.\n\nComplications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)\n\nFatal and other serious complications can occur in patients who receive\nallogeneic HSCT before or after anti–PD-1/PD-L1 treatments.\nTransplant-related complications include hyperacute graft-versus-host disease\n(GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced\nintensity conditioning, and steroid-requiring febrile syndrome (without an\nidentified infectious cause). These complications may occur despite\nintervening therapy between anti–PD-1/PD-L1 treatments and allogeneic HSCT.\nFollow patients closely for evidence of these complications and intervene\npromptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments\nprior to or after an allogeneic HSCT.\n\nIncreased Mortality in Patients With Multiple Myeloma\n\nIn trials in patients with multiple myeloma, the addition of KEYTRUDA or\nKEYTRUDA QLEX to a thalidomide analogue plus dexamethasone resulted in\nincreased mortality. Treatment of these patients with an anti–PD-1/PD-L1\ntreatment in this combination is not recommended outside of controlled trials.\n\nEmbryofetal Toxicity\n\nBased on their mechanism of action, KEYTRUDA and KEYTRUDA QLEX can each cause\nfetal harm when administered to a pregnant woman. Advise women of this\npotential risk. In females of reproductive potential, verify pregnancy status\nprior to initiating KEYTRUDA or KEYTRUDA QLEX and advise them to use effective\ncontraception during treatment and for 4 months after the last dose.\n\nAdverse Reactions\n\nIn study MK-3475A-D77, when KEYTRUDA QLEX was administered with chemotherapy\nin metastatic non–small cell lung cancer (NSCLC), serious adverse reactions\noccurred in 39% of patients. Serious adverse reactions in ≥1% of patients\nwho received KEYTRUDA QLEX were pneumonia (10%), thrombocytopenia (4%),\nfebrile neutropenia (4%), neutropenia (2.8%), musculoskeletal pain (2%),\npneumonitis (2%), diarrhea (1.6%), rash (1.2%), respiratory failure (1.2%),\nand anemia (1.2%). Fatal adverse reactions occurred in 10% of patients\nincluding pneumonia (3.2%), neutropenic sepsis (2%), death not otherwise\nspecified (1.6%), respiratory failure (1.2%), parotitis (0.4%), pneumonitis\n(0.4%), pneumothorax (0.4%), pulmonary embolism (0.4%), neutropenic colitis\n(0.4%), and seizure (0.4%). KEYTRUDA QLEX was permanently discontinued due to\nan adverse reaction in 16% of 251 patients. Adverse reactions which resulted\nin permanent discontinuation of KEYTRUDA QLEX in ≥2% of patients included\npneumonia and pneumonitis. Dosage interruptions of KEYTRUDA QLEX due to an\nadverse reaction occurred in 45% of patients. Adverse reactions which required\ndosage interruption in ≥2% of patients included neutropenia, anemia,\nthrombocytopenia, pneumonia, rash, and increased aspartate aminotransferase.\nThe most common adverse reactions (≥20%) were nausea (25%), fatigue (25%),\nand musculoskeletal pain (21%).\n\nIn KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of\n555 patients with advanced melanoma; adverse reactions leading to permanent\ndiscontinuation in more than one patient were colitis (1.4%), autoimmune\nhepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac\nfailure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were\nfatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).\n\nIn KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients\nwith stage III melanoma, KEYTRUDA was permanently discontinued due to adverse\nreactions in 14% of 509 patients; the most common (≥1%) were pneumonitis\n(1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred\nin 25% of patients receiving KEYTRUDA. The most common adverse reaction\n(≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was\nadministered as a single agent to patients with stage IIB or IIC melanoma,\nadverse reactions occurring in patients with stage IIB or IIC melanoma were\nsimilar to those occurring in 1011 patients with stage III melanoma from\nKEYNOTE-054.\n\nIn KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum\nchemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to\nadverse reactions in 20% of 405 patients. The most common adverse reactions\nresulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and\nacute kidney injury (2%). The most common adverse reactions (≥20%) with\nKEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%),\ndecreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea\n(21%), and pyrexia (20%).\n\nIn KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either\npaclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA\nwas discontinued due to adverse reactions in 15% of 101 patients. The most\nfrequent serious adverse reactions reported in at least 2% of patients were\nfebrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions\nobserved in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the\nexception that increased incidences of alopecia (47% vs 36%) and peripheral\nneuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm\ncompared to the placebo and chemotherapy arm in KEYNOTE-407.\n\nIn KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of\n636 patients with advanced NSCLC; the most common were pneumonitis (3%), death\ndue to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious\nadverse reactions reported in at least 2% of patients were pneumonia (7%),\npneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%).\nThe most common adverse reaction (≥20%) was fatigue (25%).\n\nIn KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions\nin 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis\n(1.8%). The most common adverse reactions (≥20%) were decreased appetite\n(25%), fatigue (25%), dyspnea (23%), and nausea (20%).\n\nIn KEYNOTE-671, adverse reactions occurring in patients with resectable NSCLC\nreceiving KEYTRUDA in combination with platinum-containing chemotherapy, given\nas neoadjuvant treatment and continued as single-agent adjuvant treatment,\nwere generally similar to those occurring in patients in other clinical trials\nacross tumor types receiving KEYTRUDA in combination with chemotherapy.\n\nThe most common adverse reactions (reported in ≥20%) in patients receiving\nKEYTRUDA in combination with chemotherapy or chemoradiotherapy were\nfatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash,\nvomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal\ninflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia,\nmyalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection,\nhypothyroidism, radiation skin injury, dysphagia, dry mouth, and\nmusculoskeletal pain.\n\nIn the neoadjuvant phase of KEYNOTE-671, when KEYTRUDA was administered in\ncombination with platinum-containing chemotherapy as neoadjuvant treatment,\nserious adverse reactions occurred in 34% of 396 patients. The most frequent\n(≥2%) serious adverse reactions were pneumonia (4.8%), venous\nthromboembolism (3.3%), and anemia (2%). Fatal adverse reactions occurred in\n1.3% of patients, including death due to unknown cause (0.8%), sepsis (0.3%),\nand immune-mediated lung disease (0.3%). Permanent discontinuation of any\nstudy drug due to an adverse reaction occurred in 18% of patients who received\nKEYTRUDA in combination with platinum-containing chemotherapy; the most\nfrequent adverse reactions (≥1%) that led to permanent discontinuation of\nany study drug were acute kidney injury (1.8%), interstitial lung disease\n(1.8%), anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%).\n\nOf the KEYTRUDA-treated patients who received neoadjuvant treatment, 6% of 396\npatients did not receive surgery due to adverse reactions. The most frequent\n(≥1%) adverse reaction that led to cancellation of surgery in the KEYTRUDA\narm was interstitial lung disease (1%).\n\nIn the adjuvant phase of KEYNOTE-671, when KEYTRUDA was administered as a\nsingle agent as adjuvant treatment, serious adverse reactions occurred in 14%\nof 290 patients. The most frequent serious adverse reaction was pneumonia\n(3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred. Permanent\ndiscontinuation of KEYTRUDA due to an adverse reaction occurred in 12% of\npatients who received KEYTRUDA as a single agent, given as adjuvant treatment;\nthe most frequent adverse reactions (≥1%) that led to permanent\ndiscontinuation of KEYTRUDA were diarrhea (1.7%), interstitial lung disease\n(1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain\n(1%).\n\nAdverse reactions observed in KEYNOTE-091 were generally similar to those\noccurring in other patients with NSCLC receiving KEYTRUDA as a single agent,\nwith the exception of hypothyroidism (22%), hyperthyroidism (11%), and\npneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.\n\nAdverse reactions observed in KEYNOTE-483 were generally similar to those\noccurring in other patients receiving KEYTRUDA in combination with pemetrexed\nand platinum chemotherapy.\n\nIn KEYNOTE-689, the most common adverse reactions (≥20%) in patients\nreceiving KEYTRUDA were stomatitis (48%), radiation skin injury (40%), weight\nloss (36%), fatigue (33%), dysphagia (29%), constipation (27%), hypothyroidism\n(26%), nausea (24%), rash (22%), dry mouth (22%), diarrhea (22%), and\nmusculoskeletal pain (22%).\n\nIn the neoadjuvant phase of KEYNOTE-689, of the 361 patients who received at\nleast one dose of single agent KEYTRUDA, 11% experienced serious adverse\nreactions. Serious adverse reactions that occurred in more than one patient\nwere pneumonia (1.4%), tumor hemorrhage (0.8%), dysphagia (0.6%),\nimmune-mediated hepatitis (0.6%), cellulitis (0.6%), and dyspnea (0.6%). Fatal\nadverse reactions occurred in 1.1% of patients, including respiratory failure,\nclostridium infection, septic shock, and myocardial infarction (one patient\neach). Permanent discontinuation of KEYTRUDA due to an adverse reaction\noccurred in 2.8% of patients who received KEYTRUDA as neoadjuvant treatment.\nThe most frequent adverse reaction which resulted in permanent discontinuation\nof neoadjuvant KEYTRUDA in more than one patient was arthralgia (0.6%).\n\nOf the 361 patients who received KEYTRUDA as neoadjuvant treatment, 11% did\nnot receive surgery. Surgical cancellation on the KEYTRUDA arm was due to\ndisease progression in 4%, patient decision in 3%, adverse reactions in 1.4%,\nphysician’s decision in 1.1%, unresectable tumor in 0.6%, loss of follow-up\nin 0.3%, and use of non-study anti-cancer therapy in 0.3%.\n\nOf the 323 KEYTRUDA-treated patients who received surgery following the\nneoadjuvant phase, 1.2% experienced delay of surgery (defined as on-study\nsurgery occurring ≥9 weeks after initiation of neoadjuvant KEYTRUDA) due to\nadverse reactions, and 2.8% did not receive adjuvant treatment due to adverse\nreactions.\n\nIn the adjuvant phase of KEYNOTE-689, of the 255 patients who received at\nleast one dose of KEYTRUDA, 38% experienced serious adverse reactions. The\nmost frequent serious adverse reactions reported in ≥1% of KEYTRUDA-treated\npatients were pneumonia (2.7%), pyrexia (2.4%), stomatitis (2.4%), acute\nkidney injury (2.0%), pneumonitis (1.6%), COVID-19 (1.2%), death not otherwise\nspecified (1.2%), diarrhea (1.2%), dysphagia (1.2%), gastrostomy tube site\ncomplication (1.2%), and immune-mediated hepatitis (1.2%). Fatal adverse\nreactions occurred in 5% of patients, including death not otherwise specified\n(1.2%), acute renal failure (0.4%), hypercalcemia (0.4%), pulmonary hemorrhage\n(0.4%), dysphagia/malnutrition (0.4%), mesenteric thrombosis (0.4%), sepsis\n(0.4%), pneumonia (0.4%), COVID-19 (0.4%), respiratory failure (0.4%),\ncardiovascular disorder (0.4%), and gastrointestinal hemorrhage (0.4%).\nPermanent discontinuation of adjuvant KEYTRUDA due to an adverse reaction\noccurred in 17% of patients. The most frequent (≥1%) adverse reactions that\nled to permanent discontinuation of adjuvant KEYTRUDA were pneumonitis,\ncolitis, immune-mediated hepatitis, and death not otherwise specified.\n\nIn KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in\n12% of 300 patients with HNSCC; the most common adverse reactions leading to\npermanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most\ncommon adverse reactions (≥20%) were fatigue (33%), constipation (20%), and\nrash (20%).\n\nIn KEYNOTE-048, when KEYTRUDA was administered in combination with platinum\n(cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due\nto adverse reactions in 16% of 276 patients with HNSCC. The most common\nadverse reactions resulting in permanent discontinuation of KEYTRUDA were\npneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common\nadverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation\n(37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased\nappetite (29%), stomatitis (26%), and cough (22%).\n\nIn KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of\n192 patients with HNSCC. Serious adverse reactions occurred in 45% of\npatients. The most frequent serious adverse reactions reported in at least 2%\nof patients were pneumonia, dyspnea, confusional state, vomiting, pleural\neffusion, and respiratory failure. The most common adverse reactions (≥20%)\nwere fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in\npatients with HNSCC were generally similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception\nof increased incidences of facial edema and new or worsening hypothyroidism.\n\nIn KEYNOTE-A39, when KEYTRUDA was administered in combination with enfortumab\nvedotin to patients with locally advanced or metastatic urothelial cancer\n(n=440), fatal adverse reactions occurred in 3.9% of patients, including acute\nrespiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).\nSerious adverse reactions occurred in 50% of patients receiving KEYTRUDA in\ncombination with enfortumab vedotin; the serious adverse reactions in ≥2% of\npatients were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%),\nurinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia\n(2%), and hyperglycemia (2%). Permanent discontinuation of KEYTRUDA occurred\nin 27% of patients. The most common adverse reactions (≥2%) resulting in\npermanent discontinuation of KEYTRUDA were pneumonitis/ILD (4.8%) and rash\n(3.4%). The most common adverse reactions (≥20%) occurring in patients\ntreated with KEYTRUDA in combination with enfortumab vedotin were rash (68%),\nperipheral neuropathy (67%), fatigue (51%), pruritus (41%), diarrhea (38%),\nalopecia (35%), weight loss (33%), decreased appetite (33%), nausea (26%),\nconstipation (26%), dry eye (24%), dysgeusia (21%), and urinary tract\ninfection (21%).\n\nIn KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of\n370 patients with locally advanced or metastatic urothelial carcinoma. Serious\nadverse reactions occurred in 42% of patients; those ≥2% were urinary tract\ninfection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most\ncommon adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain\n(24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea\n(20%).\n\nIn KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of\n266 patients with locally advanced or metastatic urothelial carcinoma. The\nmost common adverse reaction resulting in permanent discontinuation of\nKEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of\nKEYTRUDA-treated patients; those ≥2% were urinary tract infection,\npneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%)\nin patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain\n(32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).\n\nIn KEYNOTE-905, the most common adverse reactions (≥20%) occurring in\ncisplatin-ineligible patients with MIBC treated with KEYTRUDA in combination\nwith enfortumab vedotin (n=167) were rash (54%), pruritus (47%), fatigue\n(47%), peripheral neuropathy (39%), alopecia (35%), dysgeusia (35%), diarrhea\n(34%), constipation (28%), decreased appetite (28%), nausea (26%), urinary\ntract infection (24%), dry eye (21%), and weight loss (20%).\n\nIn the neoadjuvant phase of KEYNOTE-905, serious adverse reactions occurred in\n27% (n=167) of patients; the most frequent (≥2%) were urinary tract\ninfection (3.6%) and hematuria (2.4%). Fatal adverse reactions occurred in\n1.2% of patients, including myasthenia gravis and toxic epidermal necrolysis\n(0.6% each). Additional fatal adverse reactions were reported in 2.7% of\npatients in the post-surgery phase before adjuvant treatment started,\nincluding sepsis and intestinal obstruction (1.4% each). Permanent\ndiscontinuation of KEYTRUDA due to an adverse reaction occurred in 15% of\npatients; the most frequent (>1%) were rash (2.4%, including generalized\nexfoliative dermatitis), increased alanine aminotransferase, increased\naspartate aminotransferase, diarrhea, dysgeusia, and toxic epidermal\nnecrolysis (1.2% each). Of the 167 patients in the KEYTRUDA in combination\nwith enfortumab vedotin arm who received neoadjuvant treatment, 7 (4.2%)\npatients did not receive surgery due to adverse reactions. The adverse\nreactions that led to cancellation of surgery were acute myocardial\ninfarction, bile duct cancer, colon cancer, respiratory distress, urinary\ntract infection, and two deaths due to myasthenia gravis and toxic epidermal\nnecrolysis (0.6% each).\n\nOf the 146 patients who received neoadjuvant treatment with KEYTRUDA in\ncombination with enfortumab vedotin and underwent radical cystectomy, 6 (4.1%)\npatients experienced delay of surgery (defined as time from last neoadjuvant\ntreatment to surgery exceeding 8 weeks) due to adverse reactions.\n\nIn the adjuvant phase of KEYNOTE-905, serious adverse reactions occurred in\n43% (n=100) of patients; the most frequent (≥2%) were urinary tract\ninfection (8%); acute kidney injury and pyelonephritis (5% each); urosepsis\n(4%); and hypokalemia, intestinal obstruction, and sepsis (2% each). Fatal\nadverse reactions occurred in 7% of patients, including urosepsis,\nintracranial hemorrhage, death, myocardial infarction, multiple organ\ndysfunction syndrome, and pseudomonal pneumonia (1% each). Permanent\ndiscontinuation of KEYTRUDA due to an adverse reaction occurred in 28% of\npatients; the most frequent (>1%) were diarrhea (5%), peripheral\nneuropathy, acute kidney injury, and pneumonitis (2% each).\n\nIn KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of\n148 patients with high-risk NMIBC. The most common adverse reaction resulting\nin permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious\nadverse reactions occurred in 28% of patients; those ≥2% were pneumonia\n(3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis\n(2%), and urinary tract infection (2%). The most common adverse reactions\n(≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).\n\nAdverse reactions occurring in patients with MSI-H or dMMR CRC were similar to\nthose occurring in patients with melanoma or NSCLC who received KEYTRUDA as a\nmonotherapy.\n\nIn KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with\nMSI-H or dMMR cancer were similar to those occurring in patients with other\nsolid tumors who received KEYTRUDA as a single agent.\n\nIn KEYNOTE-811, fatal adverse reactions occurred in 3 patients who received\nKEYTRUDA in combination with trastuzumab and CAPOX (capecitabine plus\noxaliplatin) or FP (5-FU plus cisplatin) and included pneumonitis in 2\npatients and hepatitis in 1 patient. KEYTRUDA was discontinued due to adverse\nreactions in 13% of 350 patients with locally advanced unresectable or\nmetastatic HER2-positive gastric or GEJ adenocarcinoma. Adverse reactions\nresulting in permanent discontinuation of KEYTRUDA in ≥1% of patients were\npneumonitis (2.0%) and pneumonia (1.1%). In the KEYTRUDA arm vs placebo, there\nwas a difference of ≥5% incidence between patients treated with KEYTRUDA vs\nstandard of care for diarrhea (53% vs 47%), rash (35% vs 28%), hypothyroidism\n(11% vs 5%), and pneumonia (11% vs 5%).\n\nIn KEYNOTE-859, when KEYTRUDA was administered in combination with\nfluoropyrimidine- and platinum-containing chemotherapy, serious adverse\nreactions occurred in 45% of 785 patients. Serious adverse reactions in >2%\nof patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%), and\nvomiting (2.4%). Fatal adverse reactions occurred in 8% of patients who\nreceived KEYTRUDA, including infection (2.3%) and thromboembolism (1.3%).\nKEYTRUDA was permanently discontinued due to adverse reactions in 15% of\npatients. The most common adverse reactions resulting in permanent\ndiscontinuation of KEYTRUDA (≥1%) were infections (1.8%) and diarrhea\n(1.0%). The most common adverse reactions (reported in ≥20%) in patients\nreceiving KEYTRUDA in combination with chemotherapy were peripheral neuropathy\n(47%), nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased\nappetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia\nsyndrome (25%), constipation (22%), and weight loss (20%).\n\nIn KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil\nto patients with metastatic or locally advanced esophageal or GEJ (tumors with\nepicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates\nfor surgical resection or definitive chemoradiation, KEYTRUDA was discontinued\ndue to adverse reactions in 15% of 370 patients. The most common adverse\nreactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were\npneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most\ncommon adverse reactions (≥20%) with KEYTRUDA in combination with\nchemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%),\nconstipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and\nweight loss (24%).\n\nAdverse reactions occurring in patients with esophageal cancer who received\nKEYTRUDA as a monotherapy were similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a monotherapy.\n\nIn KEYNOTE-A18, when KEYTRUDA was administered with CRT (cisplatin plus\nexternal beam radiation therapy [EBRT] followed by brachytherapy [BT]) to\npatients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse reactions\noccurred in 1.4% of 294 patients, including 1 case each (0.3%) of large\nintestinal perforation, urosepsis, sepsis, and vaginal hemorrhage. Serious\nadverse reactions occurred in 34% of patients; those ≥1% included urinary\ntract infection (3.1%), urosepsis (1.4%), and sepsis (1%). KEYTRUDA was\ndiscontinued for adverse reactions in 9% of patients. The most common adverse\nreaction (≥1%) resulting in permanent discontinuation was diarrhea (1%). For\npatients treated with KEYTRUDA in combination with CRT, the most common\nadverse reactions (≥10%) were nausea (56%), diarrhea (51%), urinary tract\ninfection (35%), vomiting (34%), fatigue (28%), hypothyroidism (23%),\nconstipation (20%), weight loss (19%), decreased appetite (18%), pyrexia\n(14%), abdominal pain and hyperthyroidism (13% each), dysuria and rash (12%\neach), back and pelvic pain (11% each), and COVID-19 (10%).\n\nIn KEYNOTE-826, when KEYTRUDA was administered in combination with paclitaxel\nand cisplatin or paclitaxel and carboplatin, with or without bevacizumab\n(n=307), to patients with persistent, recurrent, or first-line metastatic\ncervical cancer regardless of tumor PD-L1 expression who had not been treated\nwith chemotherapy except when used concurrently as a radio-sensitizing agent,\nfatal adverse reactions occurred in 4.6% of patients, including 3 cases of\nhemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each\nof acute myocardial infarction, autoimmune encephalitis, cardiac arrest,\ncerebrovascular accident, femur fracture with perioperative pulmonary embolus,\nintestinal perforation, and pelvic infection. Serious adverse reactions\noccurred in 50% of patients receiving KEYTRUDA in combination with\nchemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia\n(6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury\nand sepsis (3.3% each).\n\nKEYTRUDA was discontinued in 15% of patients due to adverse reactions. The\nmost common adverse reaction resulting in permanent discontinuation (≥1%)\nwas colitis (1%).\n\nFor patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the\nmost common adverse reactions (≥20%) were peripheral neuropathy (62%),\nalopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia\n(41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each),\nconstipation and arthralgia (31% each), vomiting (30%), urinary tract\ninfection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and\ndecreased appetite (21%).\n\nFor patients treated with KEYTRUDA in combination with chemotherapy with or\nwithout bevacizumab, the most common adverse reactions (≥20%) were\nperipheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%),\ndiarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%),\nhypertension and urinary tract infection (24% each), and rash (22%).\n\nIn KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98\npatients with previously treated recurrent or metastatic cervical cancer.\nSerious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the\nmost frequent included anemia (7%), fistula, hemorrhage, and infections\n[except urinary tract infections] (4.1% each). The most common adverse\nreactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea\n(23%), pain and abdominal pain (22% each), and decreased appetite (21%).\n\nIn KEYNOTE-394, KEYTRUDA was discontinued due to adverse reactions in 13% of\n299 patients with previously treated hepatocellular carcinoma. The most common\nadverse reaction resulting in permanent discontinuation of KEYTRUDA was\nascites (2.3%). The most common adverse reactions in patients receiving\nKEYTRUDA (≥10%) were pyrexia (18%), rash (18%), diarrhea (16%), decreased\nappetite (15%), pruritus (12%), upper respiratory tract infection (11%), cough\n(11%), and hypothyroidism (10%).\n\nIn KEYNOTE-966, when KEYTRUDA was administered in combination with gemcitabine\nand cisplatin, KEYTRUDA was discontinued for adverse reactions in 15% of 529\npatients with locally advanced unresectable or metastatic biliary tract\ncancer. The most common adverse reaction resulting in permanent\ndiscontinuation of KEYTRUDA (≥1%) was pneumonitis (1.3%). Adverse reactions\nleading to the interruption of KEYTRUDA occurred in 55% of patients. The most\ncommon adverse reactions or laboratory abnormalities leading to interruption\nof KEYTRUDA (≥2%) were decreased neutrophil count (18%), decreased platelet\ncount (10%), anemia (6%), decreased white blood cell count (4%), pyrexia\n(3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased\nAST (2.5%), and biliary obstruction (2.3%).\n\nIn KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with\nMCC (n=105) were generally similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a single agent.\n\nIn KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib,\nfatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse\nreactions occurred in 40% of patients, the most frequent (≥1%) were\nhepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration\n(1%), and pneumonitis (1%). Permanent discontinuation due to an adverse\nreaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only\n(13%), and the combination (8%); the most common were hepatotoxicity (13%),\ndiarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular\naccident (1.2%). The most common adverse reactions (≥20%) were diarrhea\n(56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%),\nhypothyroidism (35%), decreased appetite (30%), palmar-plantar\nerythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%),\ndysphonia (25%), rash (25%), cough (21%), and constipation (21%).\n\nIn KEYNOTE-564, when KEYTRUDA was administered as a single agent for the\nadjuvant treatment of renal cell carcinoma, serious adverse reactions occurred\nin 20% of patients receiving KEYTRUDA; the serious adverse reactions (≥1%)\nwere acute kidney injury, adrenal insufficiency, pneumonia, colitis, and\ndiabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2%\nincluding 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse\nreactions occurred in 21% of 488 patients; the most common (≥1%) were\nincreased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most\ncommon adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue\n(40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).\n\nIn KEYNOTE-868, when KEYTRUDA was administered in combination with\nchemotherapy (paclitaxel and carboplatin) to patients with advanced or\nrecurrent endometrial carcinoma (n=382), serious adverse reactions occurred in\n35% of patients receiving KEYTRUDA in combination with chemotherapy, compared\nto 19% of patients receiving placebo in combination with chemotherapy (n=377).\nFatal adverse reactions occurred in 1.6% of patients receiving KEYTRUDA in\ncombination with chemotherapy, including COVID-19 (0.5%) and cardiac arrest\n(0.3%). KEYTRUDA was discontinued for an adverse reaction in 14% of patients.\nAdverse reactions occurring in patients treated with KEYTRUDA and chemotherapy\nwere generally similar to those observed with KEYTRUDA alone or chemotherapy\nalone, with the exception of rash (33% all Grades; 2.9% Grades 3-4).\n\nAdverse reactions occurring in patients with MSI-H or dMMR endometrial\ncarcinoma who received KEYTRUDA as a single agent were similar to those\noccurring in patients with melanoma or NSCLC who received KEYTRUDA as a single\nagent.\n\nAdverse reactions occurring in patients with recurrent or metastatic cSCC or\nlocally advanced cSCC were similar to those occurring in patients with\nmelanoma or NSCLC who received KEYTRUDA as a monotherapy.\n\nIn KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy\n(carboplatin and paclitaxel followed by doxorubicin or epirubicin and\ncyclophosphamide) followed by surgery and continued adjuvant treatment with\nKEYTRUDA as a single agent (n=778) to patients with newly diagnosed,\npreviously untreated, high-risk early-stage TNBC, fatal adverse reactions\noccurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune\nencephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and\nsepsis in association with multiple organ dysfunction syndrome and myocardial\ninfarction. Serious adverse reactions occurred in 44% of patients receiving\nKEYTRUDA; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia\n(2.6%), and neutropenia (2.2%). KEYTRUDA was discontinued in 20% of patients\ndue to adverse reactions. The most common reactions (≥1%) resulting in\npermanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and\nrash (1%). The most common adverse reactions (≥20%) in patients receiving\nKEYTRUDA with chemotherapy followed by KEYTRUDA alone were fatigue (70%),\nnausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and\nperipheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache\n(30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%),\ndecreased appetite (23%), insomnia (21%), and myalgia (20%).\n\nIn KEYNOTE-D19, when KEYTRUDA was administered in combination with sacituzumab\ngovitecan-hziy to patients with unresectable locally advanced or metastatic\nTNBC who had not been previously treated with systemic therapy for advanced\ndisease and whose tumors express PD-L1 (n=221), fatal adverse reactions\noccurred in 3.2% of patients, including death due to unknown cause (0.9%),\ncompleted suicide, neutropenic sepsis, sepsis, pneumonia, and pulmonary\nembolism (0.5% each).\n\nSerious adverse reactions occurred in 38% of patients receiving KEYTRUDA in\ncombination with sacituzumab govitecan-hziy. Serious adverse reactions in\n≥2% of patients were febrile neutropenia (7%), neutropenia (6%), diarrhea\n(5%), fatigue and pneumonia (2.3% each).\n\nPermanent discontinuation of KEYTRUDA due to an adverse reaction occurred in\n9% of patients. The adverse reactions which resulted in permanent\ndiscontinuation of KEYTRUDA most commonly (≥1%) were pneumonitis and rash\n(1.4% each).\n\nAdverse reactions leading to the interruption of KEYTRUDA occurred in 44% of\npatients. The most common adverse reactions leading to interruption of\nKEYTRUDA in ≥2% were urinary tract infection (3.9%), adrenal insufficiency\n(2.6%), pyrexia (2.6%), pneumonitis (2.6%), upper respiratory tract infection\n(2.6%), neutropenia (2.1%), diarrhea (2.1%) and COVID-19 (2.1%).\n\nThe most common (≥25%) adverse reactions, including laboratory\nabnormalities, occurring in patients treated with KEYTRUDA in combination with\nsacituzumab govitecan-hziy were decreased neutrophil count and decreased\nhemoglobin (86% each), decreased leukocyte count (84%), diarrhea (72%), nausea\n(68%), decreased lymphocyte count (61%), fatigue (58%), alopecia (52%),\nincreased alkaline phosphatase and increased glucose (50% each), increased\nalanine aminotransferase (47%), constipation (41%), increased aspartate\naminotransferase (40%), rash (37%), decreased potassium (35%), increased\nlactate dehydrogenase (34%), vomiting (29%), abdominal pain, headache, and\nincreased eosinophils, (26% each), and decreased albumin (25%).\n\nIn KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel\nprotein-bound, or gemcitabine and carboplatin) were administered to patients\nwith locally recurrent unresectable or metastatic TNBC who had not been\npreviously treated with chemotherapy in the metastatic setting (n=596), fatal\nadverse reactions occurred in 2.5% of patients, including cardio-respiratory\narrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in\n30% of patients receiving KEYTRUDA in combination with chemotherapy; the\nserious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and\nthrombocytopenia (2%). KEYTRUDA was discontinued in 11% of patients due to\nadverse reactions. The most common reactions resulting in permanent\ndiscontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and\npneumonitis (1.2%). The most common adverse reactions (≥20%) in patients\nreceiving KEYTRUDA in combination with chemotherapy were fatigue (48%), nausea\n(44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash\n(26% each), cough (23%), decreased appetite (21%), and headache (20%).\n\nIn KEYNOTE-B96, when KEYTRUDA in combination with paclitaxel, with or without\nbevacizumab, was administered to patients with epithelial ovarian, fallopian\ntube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1),\nserious adverse reactions occurred in 54% of patients receiving KEYTRUDA and\npaclitaxel with or without bevacizumab. Serious adverse reactions in ≥2% of\npatients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal\ninsufficiency, hyponatremia (3% each), COVID-19, decreased neutrophil count,\npulmonary embolism (2.6% each), abdominal pain, anemia, colitis, diarrhea,\nfebrile neutropenia, pyrexia, and vomiting (2.1% each).\n\nFatal adverse reactions occurred in 3.9% of patients receiving KEYTRUDA and\npaclitaxel, with or without bevacizumab, including assisted suicide (0.9%),\ndeath, intestinal perforation, sepsis, COVID-19, cardio-respiratory arrest,\ncolitis, and embolic stroke (0.4% each).\n\nKEYTRUDA was permanently discontinued for adverse reactions in 16% of\npatients. The most common adverse reactions resulting in permanent\ndiscontinuation of KEYTRUDA (≥1%) were colitis and increased alanine\naminotransferase (1.3% each). Adverse reactions leading to the interruption of\nKEYTRUDA occurred in 44% of patients. The most common adverse reactions\nleading to interruption of KEYTRUDA in ≥2% were urinary tract infection\n(3.9%), adrenal insufficiency, pyrexia, pneumonitis, upper respiratory tract\ninfection (2.6% each), neutropenia, diarrhea, and COVID-19 (2.1% each).\n\nThe most common adverse reactions (≥20%) for patients treated with KEYTRUDA\nin combination with paclitaxel, with or without bevacizumab, were diarrhea\n(45%), fatigue (43%), nausea (41%), alopecia, peripheral neuropathy (38%\neach), epistaxis (31%), urinary tract infection (27%), constipation (25%),\nabdominal pain, decreased appetite, vomiting (24% each), hypothyroidism (21%),\ncough, hypertension, and rash (20% each).\n\nFor patients treated with KEYTRUDA in combination with paclitaxel and\nbevacizumab (N=169), decreased white blood cell count (27%), stomatitis (22%),\nand pyrexia (21%) were also reported as adverse reactions.\n\nLactation\n\nBecause of the potential for serious adverse reactions in breastfed children,\nadvise women not to breastfeed during treatment and for 4 months after the\nlast dose.\n\nPediatric Use\n\nIn KEYNOTE-051, 173 pediatric patients (65 pediatric patients aged 6 months to\nyounger than 12 years and 108 pediatric patients aged 12 years to 17 years)\nwere administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of\nexposure was 2.1 months (range: 1 day to 25 months).\n\nThe safety and effectiveness of KEYTRUDA QLEX for the treatment of pediatric\npatients 12 years and older who weigh greater than 40 kg have been established\nfor:\n\n\n * Stage IIB, IIC, or III melanoma following complete resection\n\n * Unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch\nrepair deficient (dMMR) solid tumors\n\n * Recurrent locally advanced or metastatic Merkel cell carcinoma\n\nUse of KEYTRUDA QLEX in pediatric patients for these indications is supported\nby evidence from adequate and well-controlled studies of KEYTRUDA in adults\nand additional pharmacokinetic and safety data for KEYTRUDA in pediatric\npatients 12 years and older. Pembrolizumab exposures in pediatric patients 12\nyears and older who weigh greater than 40 kg are predicted to be within range\nof those observed in adults at the same dosage.\n\nThe safety and effectiveness of KEYTRUDA as a single agent have been\nestablished in pediatric patients with melanoma (stage IIB, IIC, or III\nmelanoma following complete resection in pediatric patients 12 and older),\nMCC, MSI-H or dMMR cancer.\n\nUse of KEYTRUDA in pediatric patients for these indications is supported by\nevidence from adequate and well-controlled studies in adults with additional\npharmacokinetic and safety data in pediatric patients.\n\nThe safety and effectiveness of KEYTRUDA QLEX have not been established in\npediatric patients younger than 12 years of age for the treatment of melanoma,\nMCC, MSI-H or dMMR cancer.\n\nThe safety and effectiveness of KEYTRUDA and KEYTRUDA QLEX have not been\nestablished in pediatric patients for other approved indications shown.\n\nAdverse reactions that occurred at a ≥10% higher rate in pediatric patients\nwhen compared to adults were pyrexia (33%), leukopenia (30%), vomiting (29%),\nneutropenia (28%), headache (25%), abdominal pain (23%), thrombocytopenia\n(22%), Grade 3 anemia (17%), decreased lymphocyte count (13%), and decreased\nwhite blood cell count (11%).\n\nGeriatric Use\n\nOf the 564 patients with locally advanced or metastatic urothelial cancer\ntreated with KEYTRUDA in combination with enfortumab vedotin, 44% (n=247) were\n65-74 years and 26% (n=144) were 75 years or older. No overall differences in\neffectiveness were observed between patients 65 years of age or older and\nyounger patients. Patients 75 years of age or older treated with KEYTRUDA in\ncombination with enfortumab vedotin experienced a higher incidence of fatal\nadverse reactions than younger patients. The incidence of fatal adverse\nreactions was 4% in patients younger than 75 and 7% in patients 75 years or\nolder.\n\nOf the 167 patients with MIBC treated with KEYTRUDA in combination with\nenfortumab vedotin, 37% (n=61) were 65-74 years and 46% (n=77) were 75 years\nor older. Patients 75 years of age or older treated with KEYTRUDA in\ncombination with enfortumab vedotin experienced a higher incidence of fatal\nadverse reactions than younger patients. The incidence of fatal adverse\nreactions was 4% in patients younger than 75 and 12% in patients 75 years or\nolder.\n\nAdditional Selected Indications in the U.S. for KEYTRUDA and KEYTRUDA QLEX\n\nMelanoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with unresectable or metastatic melanoma.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the adjuvant treatment of\nadult and pediatric patients 12 years and older with stage IIB, IIC, or III\nmelanoma following complete resection.\n\nNon-Small Cell Lung Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with pemetrexed\nand platinum chemotherapy, for the first-line treatment of adult patients with\nmetastatic nonsquamous non–small cell lung cancer (NSCLC), with no EGFR or\nALK genomic tumor aberrations.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with carboplatin\nand either paclitaxel or paclitaxel protein-bound, for the first-line\ntreatment of adult patients with metastatic squamous NSCLC.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\nfirst-line treatment of adult patients with NSCLC expressing PD-L1 [tumor\nproportion score (TPS) ≥1%] as determined by an FDA-authorized test, with no\nEGFR or ALK genomic tumor aberrations, and is:\n\n\n * stage III where patients are not candidates for surgical resection or\ndefinitive chemoradiation, or\n\n * metastatic.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with metastatic NSCLC whose tumors express PD-L1\n(TPS ≥1%) as determined by an FDA-authorized test, with disease progression\non or after platinum-containing chemotherapy. Patients with EGFR or ALK\ngenomic tumor aberrations should have disease progression on FDA-authorized\ntherapy for these aberrations prior to receiving KEYTRUDA or KEYTRUDA QLEX.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with resectable (tumors ≥4 cm or node positive) NSCLC in\ncombination with platinum-containing chemotherapy as neoadjuvant treatment,\nand then continued as a single agent as adjuvant treatment after surgery.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated as adjuvant\ntreatment following resection and platinum-based chemotherapy for adult\npatients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.\n\nMalignant Pleural Mesothelioma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with pemetrexed\nand platinum chemotherapy, for the first-line treatment of adult patients with\nunresectable advanced or metastatic malignant pleural mesothelioma (MPM).\n\nHead and Neck Squamous Cell Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with resectable locally advanced head and neck squamous cell\ncarcinoma (HNSCC) whose tumors express PD-L1 [Combined Positive Score (CPS)\n≥1] as determined by an FDA-authorized test, as a single agent as\nneoadjuvant treatment, continued as adjuvant treatment in combination with\nradiotherapy (RT) with or without cisplatin and then as a single agent.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with platinum\nand fluorouracil (FU), for the first-line treatment of adult patients with\nmetastatic or with unresectable, recurrent head and neck squamous cell\ncarcinoma (HNSCC).\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\nfirst-line treatment of adult patients with metastatic or with unresectable,\nrecurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by an\nFDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with recurrent or metastatic head and neck\nsquamous cell carcinoma (HNSCC) with disease progression on or after\nplatinum-containing chemotherapy.\n\nUrothelial Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with enfortumab\nvedotin, for the treatment of adult patients with locally advanced or\nmetastatic urothelial cancer.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with locally advanced or metastatic urothelial\ncarcinoma:\n\n\n * who are not eligible for any platinum-containing chemotherapy, or\n\n * who have disease progression during or following platinum-containing\nchemotherapy or within 12 months of neoadjuvant or adjuvant treatment with\nplatinum-containing chemotherapy.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with enfortumab\nvedotin, as neoadjuvant treatment and then continued after cystectomy as\nadjuvant treatment for the treatment of adult patients with muscle invasive\nbladder cancer (MIBC) who are ineligible for cisplatin-containing\nchemotherapy.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with Bacillus Calmette-Guerin (BCG)-unresponsive,\nhigh-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ\n(CIS) with or without papillary tumors who are ineligible for or have elected\nnot to undergo cystectomy.\n\nMicrosatellite Instability-High or Mismatch Repair Deficient Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with unresectable or metastatic microsatellite instability-high\n(MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an\nFDA-authorized test, that have progressed following prior treatment and who\nhave no satisfactory alternative treatment options. For this indication,\nKEYTRUDA also is indicated for the treatment of pediatric patients, and\nKEYTRUDA QLEX also is indicated for the treatment of pediatric patients 12\nyears and older.\n\nMicrosatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC)\nas determined by an FDA-authorized.\n\nGastric Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\ntrastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the\nfirst-line treatment of adults with locally advanced unresectable or\nmetastatic HER2-positive gastric or gastroesophageal junction (GEJ)\nadenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an\nFDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nfluoropyrimidine- and platinum-containing chemotherapy, for the first-line\ntreatment of adults with locally advanced unresectable or metastatic\nHER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose\ntumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test.\n\nEsophageal Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with locally advanced or metastatic esophageal or gastroesophageal\njunction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ)\ncarcinoma that is not amenable to surgical resection or definitive\nchemoradiation either:\n\n\n * in combination with platinum- and fluoropyrimidine-based chemotherapy for\npatients with tumors that express PD-L1 (CPS ≥1), or\n\n * as a single agent after one or more prior lines of systemic therapy for\npatients with tumors of squamous cell histology that express PD-L1 (CPS ≥10)\nas determined by an FDA-authorized test.\n\nCervical Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nchemoradiotherapy (CRT), for the treatment of adult patients with locally\nadvanced cervical cancer involving the lower third of the vagina, with or\nwithout extension to pelvic sidewall, or hydronephrosis/non-functioning\nkidney, or spread to adjacent pelvic organs (FIGO 2014 Stage III-IVA).\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with\nchemotherapy, with or without bevacizumab, for the treatment of adult patients\nwith persistent, recurrent, or metastatic cervical cancer whose tumors express\nPD-L1 (CPS ≥1) as determined by an FDA-authorized test.\n\nKEYTRUDA and KEYTRUDA QLEX, as single agents, are each indicated for the\ntreatment of adult patients with recurrent or metastatic cervical cancer with\ndisease progression on or after chemotherapy whose tumors express PD-L1 (CPS\n≥1) as determined by an FDA-authorized test.\n\nHepatocellular Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have\nreceived prior systemic therapy other than a PD-1/PD-L1–containing regimen.\n\nBiliary Tract Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with gemcitabine\nand cisplatin, for the treatment of adult patients with locally advanced\nunresectable or metastatic biliary tract cancer (BTC).\n\nMerkel Cell Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with recurrent locally advanced or metastatic Merkel cell carcinoma\n(MCC). For this indication, KEYTRUDA also is indicated for the treatment of\npediatric patients, and KEYTRUDA QLEX also is indicated for the treatment of\npediatric patients 12 years and older.\n\nRenal Cell Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with axitinib,\nfor the first-line treatment of adult patients with advanced renal cell\ncarcinoma (RCC).\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the adjuvant treatment of\nadult patients with renal cell carcinoma (RCC) at intermediate high or high\nrisk of recurrence following nephrectomy, or following nephrectomy and\nresection of metastatic lesions.\n\nEndometrial Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with carboplatin\nand paclitaxel, followed by KEYTRUDA or KEYTRUDA QLEX as a single agent, for\nthe treatment of adult patients with primary advanced or recurrent endometrial\ncarcinoma.\n\nKEYTRUDA and KEYTRUDA QLEX, as a single agent, are each indicated for the\ntreatment of adult patients with advanced endometrial carcinoma that is MSI-H\nor dMMR, as determined by an FDA-authorized test, who have disease progression\nfollowing prior systemic therapy in any setting and are not candidates for\ncurative surgery or radiation.\n\nCutaneous Squamous Cell Carcinoma\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated for the treatment of adult\npatients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC)\nor locally advanced cSCC that is not curable by surgery or radiation.\n\nOvarian Cancer\n\nKEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with paclitaxel,\nwith or without bevacizumab, for the treatment of adult patients with\nplatinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal\ncarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an\nFDA-authorized test, and who have received 1 or 2 prior systemic treatment\nregimens.\n\nAbout the Merck Access Program for KEYTRUDA and KEYTRUDA QLEX\n\nAt Merck, we are committed to supporting accessibility to our cancer\nmedicines. Merck provides multiple programs to help appropriate patients who\nare prescribed KEYTRUDA or KEYTRUDA QLEX have access to our anti-PD-1\ntherapies. The Merck Access Program provides reimbursement support for\npatients receiving KEYTRUDA and KEYTRUDA QLEX, including information to help\nwith out-of-pocket costs and co-pay assistance for eligible patients. More\ninformation is available by calling 855-257-3932 or visiting\nhttps://www.merckaccessprogram.com/\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merckaccessprogram.com%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merckaccessprogram.com%2F&index=3&md5=059c60549589d033b9240f26999048fe)\n.\n\nAbout Merck’s Patient Support Program for KEYTRUDA and KEYTRUDA QLEX\n\nMerck is committed to helping provide patients and their caregivers support\nthroughout their treatment with KEYTRUDA and KEYTRUDA QLEX. The My Merck\nSupport Program provides a range of resources and support. For further\ninformation and to sign up, eligible patients may call 888-55-MyMRK\n(888-556-9675) or visit https://www.mymercksupportteam.com/\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.mymercksupportteam.com%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.mymercksupportteam.com%2F&index=4&md5=abe90bdac879eb7e687d5b73322fb940)\n.\n\nMerck’s focus on cancer\n\nEvery day, we follow the science as we work to discover innovations that can\nhelp patients, no matter what stage of cancer they have. As a leading oncology\ncompany, we are pursuing research where scientific opportunity and medical\nneed converge, underpinned by our diverse pipeline of more than 20 novel\nmechanisms. With one of the largest clinical development programs across more\nthan 30 tumor types, we strive to advance breakthrough science that will shape\nthe future of oncology. By addressing barriers to clinical trial\nparticipation, screening and treatment, we work with urgency to reduce\ndisparities and help ensure patients have access to high-quality cancer care.\nOur unwavering commitment is what will bring us closer to our goal of bringing\nlife to more patients with cancer. For more information, visit\nwww.merck.com/research/oncology\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merck.com%2Fresearch%2Foncology%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=www.merck.com%2Fresearch%2Foncology&index=5&md5=74f28dc8203d173c2a76036ec0da13c6)\n.\n\nAbout Merck\n\nAt Merck, known as MSD outside of the United States and Canada, we are unified\naround our purpose: We use the power of leading-edge science to save and\nimprove lives around the world. For more than 130 years, we have brought hope\nto humanity through the development of important medicines and vaccines. We\naspire to be the premier research-intensive biopharmaceutical company in the\nworld – and today, we are at the forefront of research to deliver innovative\nhealth solutions that advance the prevention and treatment of diseases in\npeople and animals. We foster a diverse and inclusive global workforce and\noperate responsibly every day to enable a safe, sustainable and healthy future\nfor all people and communities. For more information, visit www.merck.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merck.com%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=www.merck.com&index=6&md5=a6c73ebbc30ae20ad211a6fd5401af97)\nand connect with us on X (formerly Twitter)\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fx.com%2FMerck&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=X+%28formerly+Twitter%29&index=7&md5=127b73bddc888fe11ea5055802293338)\n, Facebook\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.facebook.com%2FMerckInvents%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=Facebook&index=8&md5=f8bd48911e3ea0d59c059e574fff2930)\n, Instagram\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.instagram.com%2Fmerck%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=Instagram&index=9&md5=fb45d4d72b1c4ecbe7cd694fd530ecf1)\n, YouTube\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.youtube.com%2FMerck&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=YouTube&index=10&md5=986f3f8d8649ec56a62f1feb7aa4d8b2)\nand LinkedIn\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.linkedin.com%2Fcompany%2Fmerck&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=LinkedIn&index=11&md5=d95aef98a495c9ceb70781e085f3fa54)\n.\n\nForward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA\n\nThis news release of Merck & Co., Inc., Rahway, N.J., USA (the\n“company”) includes “forward-looking statements” within the meaning of\nthe safe harbor provisions of the U.S. Private Securities Litigation Reform\nAct of 1995. These statements are based upon the current beliefs and\nexpectations of the company’s management and are subject to significant\nrisks and uncertainties. There can be no guarantees with respect to pipeline\ncandidates that the candidates will receive the necessary regulatory approvals\nor that they will prove to be commercially successful. If underlying\nassumptions prove inaccurate or risks or uncertainties materialize, actual\nresults may differ materially from those set forth in the forward-looking\nstatements.\n\nRisks and uncertainties include but are not limited to, general industry\nconditions and competition; general economic factors, including interest rate\nand currency exchange rate fluctuations; the impact of pharmaceutical industry\nregulation and health care legislation in the United States and\ninternationally; global trends toward health care cost containment;\ntechnological advances, new products and patents attained by competitors;\nchallenges inherent in new product development, including obtaining regulatory\napproval; the company’s ability to accurately predict future market\nconditions; manufacturing difficulties or delays; financial instability of\ninternational economies and sovereign risk; dependence on the effectiveness of\nthe company’s patents and other protections for innovative products; and the\nexposure to litigation, including patent litigation, and/or regulatory\nactions.\n\nThe company undertakes no obligation to publicly update any forward-looking\nstatement, whether as a result of new information, future events or otherwise.\nAdditional factors that could cause results to differ materially from those\ndescribed in the forward-looking statements can be found in the company’s\nAnnual Report on Form 10-K for the year ended December 31, 2025 and the\ncompany’s other filings with the Securities and Exchange Commission (SEC)\navailable at the SEC’s Internet site (www.sec.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.sec.gov%2F&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=www.sec.gov&index=12&md5=d2128632e9d9d305d7a933d2c2373576)\n).\n\nPlease see Prescribing Information for KEYTRUDA (pembrolizumab) at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fnam11.safelinks.protection.outlook.com%2F%3Furl%3Dhttps%253A%252F%252Fwww.merck.com%252Fproduct%252Fusa%252Fpi_circulars%252Fk%252Fkeytruda%252Fkeytruda_pi.pdf%26data%3D05%257C02%257Crmccarthy%2540realchemistry.com%257Ccc208a38b1524f6a5d0d08ded23aeec8%257C6fa5bfc4f95843f8bb395d382689654b%257C0%257C0%257C639179347744745628%257CUnknown%257CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%253D%253D%257C0%257C%257C%257C%26sdata%3DzjOHvlV1gS%252Fp5gWmwPZHgyFDhbGn58NqR6J2ohVfMgE%253D%26reserved%3D0&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda%2Fkeytruda_pi.pdf&index=13&md5=74e8fe4b4793ec499a3682247021daa8)\nand Medication Guide for KEYTRUDA at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda%2Fkeytruda_mg.pdf&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda%2Fkeytruda_mg.pdf&index=14&md5=5dca1a1969ace58179e1556e18150fbe)\n.\n\nPlease see Prescribing Information for KEYTRUDA QLEX™ (pembrolizumab and\nberahyaluronidase alfa-pmph) at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda_qlex/keytruda_qlex_pi.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fnam11.safelinks.protection.outlook.com%2F%3Furl%3Dhttps%253A%252F%252Fwww.merck.com%252Fproduct%252Fusa%252Fpi_circulars%252Fk%252Fkeytruda_qlex%252Fkeytruda_qlex_pi.pdf%26data%3D05%257C02%257Crmccarthy%2540realchemistry.com%257Ccc208a38b1524f6a5d0d08ded23aeec8%257C6fa5bfc4f95843f8bb395d382689654b%257C0%257C0%257C639179347744814207%257CUnknown%257CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%253D%253D%257C0%257C%257C%257C%26sdata%3DVxl2Q6NHtpc2J0yigwdC0utC42UEg2%252BMkYSyMoGTEGk%253D%26reserved%3D0&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda_qlex%2Fkeytruda_qlex_pi.pdf&index=15&md5=b537f1146b36e9308440e81a29791b8b)\nand Medication Guide for KEYTRUDA QLEX™ at\nhttps://www.merck.com/product/usa/pi_circulars/k/keytruda_qlex/keytruda_qlex_mg.pdf\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fnam11.safelinks.protection.outlook.com%2F%3Furl%3Dhttps%253A%252F%252Fwww.merck.com%252Fproduct%252Fusa%252Fpi_circulars%252Fk%252Fkeytruda_qlex%252Fkeytruda_qlex_mg.pdf%26data%3D05%257C02%257Crmccarthy%2540realchemistry.com%257Ccc208a38b1524f6a5d0d08ded23aeec8%257C6fa5bfc4f95843f8bb395d382689654b%257C0%257C0%257C639179347744835582%257CUnknown%257CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%253D%253D%257C0%257C%257C%257C%26sdata%3DAa6luv5n7H%252FNLMU4UrON1MSRCWtWIUX%252BTQxJ6vybkgc%253D%26reserved%3D0&esheet=54559942&newsitemid=20260625926870&lan=en-US&anchor=https%3A%2F%2Fwww.merck.com%2Fproduct%2Fusa%2Fpi_circulars%2Fk%2Fkeytruda_qlex%2Fkeytruda_qlex_mg.pdf&index=16&md5=8b5d3b802f2a649565531475514e251d)\n.\n\n\n\nView source version on businesswire.com:\nhttps://www.businesswire.com/news/home/20260625926870/en/\n(https://www.businesswire.com/news/home/20260625926870/en/)\n\nMedia Contacts:\n\nJulie Cunningham\n\n(617) 519-6264\n\nDiane Foley\n\n(862) 260-0060\n\nInvestor Contacts:\n\nPeter Dannenbaum\n\n(732) 594-1579\n\nSteven Graziano\n\n(732) 594-1583\n\n\nCopyright Business Wire 2026"},"type":"article","timestamp":"2026-06-25T10:45:00.355899741Z","server_sent_at_ms":1782384300355},"received_at":"2026-06-25T10:45:00.698Z","source_url":"https://www.businesswire.com/news/home/20260625926870/en/"},"analysis":{"id":"62295","press_release_id":"72926","analysis_json":{"industry":{"label":"Pharmaceuticals","sector":"Health Care"},"redFlags":[],"eventType":"fda_approval","narrative":"Merck announced FDA approval of KEYTRUDA and its subcutaneous formulation KEYTRUDA QLEX, each in combination with Gilead's Trodelvy, for first-line treatment of PD-L1-positive advanced triple-negative breast cancer.\n\nThe approvals are based on Phase 3 KEYNOTE-D19/ASCENT-04 data showing the regimen reduced the risk of disease progression or death by 35% and achieved a median PFS of 11.2 months compared to 7.8 months for the chemotherapy combination.\n\nThis marks the first approval of a PD-1 inhibitor combined with a Trop-2-directed antibody-drug conjugate in this setting, creating a potentially practice-changing option for patients with limited treatment choices.","sentiment":"bullish","agentHooks":{"shouldPost":true,"suggestedAngle":"Merck secures first-line TNBC approval for KEYTRUDA + Trodelvy combo, significantly bolstering its oncology portfolio."},"keyFigures":{"drugName":"KEYTRUDA","phaseOfTrial":"Phase 3","customDimensions":{"p_value":0.0009,"orr_percent":61,"hazard_ratio":0.65,"median_pfs_months":11.2,"cr_control_percent":8,"pfs_control_months":7.8,"confidence_interval":"95% CI, 0.51-0.84","orr_control_percent":55,"risk_reduction_percent":35,"complete_response_percent":12}},"quotedText":"Today’s approvals of KEYTRUDA and KEYTRUDA QLEX each in combination with Trodelvy represent a meaningful milestone for those living with advanced TNBC.","namedEntities":{"people":[{"name":"Sara Tolaney","role":"Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and principal investigator"},{"name":"Gursel Aktan","role":"Vice President, Global Clinical Development, Merck Research Laboratories"},{"name":"Ricki Fairley","role":"Co-founder and CEO of TOUCH, The Black Breast Cancer Alliance"}],"products":["KEYTRUDA","pembrolizumab","KEYTRUDA QLEX","Trodelvy","sacituzumab govitecan-hziy","berahyaluronidase alfa-pmph"],"companies":[{"name":"Merck","ticker":"MRK"},{"name":"Gilead Sciences","ticker":"GILD","relationship":"partner"},{"name":"Dana-Farber Cancer Institute","relationship":"research institution"},{"name":"TOUCH, The Black Breast Cancer Alliance","relationship":"advocacy group"},{"name":"National Comprehensive Cancer Network","relationship":"standards 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