{"success":true,"data":{"pressRelease":{"id":"37051","rtpr_id":"nBw4Zt4QQa","ticker":"4568","exchange":"TSE Tokyo","all_tickers":["4568"],"title":"Enhertu® Approved in the U.S. for Two New Indications for Patients with HER2 Positive Early Breast Cancer","author":"Business Wire","published_at":"2026-05-15T22:31:00.078Z","article_body":"Enhertu(®) Approved in the U.S. for Two New Indications for Patients with\nHER2 Positive Early Breast Cancer\n\n\n * Approved for use before surgery based on DESTINY-Breast11 phase 3 trial or\nfollowing surgery based on DESTINY-Breast05 phase 3 trial\n\n * Two new indications bring Daiichi Sankyo and AstraZeneca’s Enhertu into\ncurative-intent setting, reinforcing its role across stages of HER2 positive\nbreast cancer\n\n * Enhertu now approved for nine indications with six across both early and\nmetastatic HER2 positive breast cancer\n\nEnhertu(®) (fam-trastuzumab deruxtecan-nxki) has been approved by the U.S.\nFood and Drug Administration (FDA) for two new breast cancer indications in\nthe neoadjuvant and adjuvant settings of patients with HER2 positive early\nbreast cancer.\n\nIn the neoadjuvant setting, Enhertu followed by a taxane, trastuzumab and\npertuzumab (THP) has been approved for the treatment of adult patients with\nHER2 positive stage 2 or stage 3 breast cancer. In the adjuvant setting,\nEnhertu has been approved for the treatment of adult patients with HER2\npositive breast cancer who have residual invasive disease following\nneoadjuvant trastuzumab (with or without pertuzumab) and taxane-based\ntreatment.\n\nEnhertu is a specifically engineered HER2 directed DXd antibody drug conjugate\n(ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and\ncommercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/NYSE: AZN).\n\nThe neoadjuvant approval was based on results from the DESTINY-Breast11\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast11&index=1&md5=9998b6f4b4475479b61fe7eddaec6776)\nphase 3 trial published in Annals of Oncology\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252825%252904968-3%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Annals+of+Oncology&index=2&md5=5ddfb4de9c9bc01f6979dce342e9488a)\nand the adjuvant approval was based on the results from the DESTINY-Breast05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast05&index=3&md5=90e7d01504612a8f7dfcefbe8377119a)\nphase 3 trial published in The New England Journal of Medicine\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nejm.org%2F&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=The+New+England+Journal+of+Medicine&index=4&md5=eda21a0ee9da940d0b458b4b894a5b12)\n.( )Data from both trials were presented at the 2025 European Society for\nMedical Oncology (ESMO) Congress.\n\nIn DESTINY-Breast11, Enhertu followed by THP demonstrated a statistically\nsignificant and clinically meaningful improvement in the pathologic complete\nresponse (pCR) rate compared to dose-dense doxorubicin and cyclophosphamide\nfollowed by THP (ddAC-THP) in patients with high-risk, locally advanced HER2\npositive early-stage breast cancer. Pathologic complete response is defined as\nno evidence of invasive cancer cells in the removed breast tissue and lymph\nnodes following treatment. The pCR rate with Enhertu followed by THP was 67.3%\ncompared with 56.3% with ddAC-THP, representing a difference of 11.2% (95%\nconfidence interval [CI]: 3.9-18.3; p=0.003).\n\nIn DESTINY-Breast05, Enhertu significantly reduced the risk of invasive\ndisease recurrence or death (invasive disease-free survival [IDFS]) by 53%\n(hazard ratio [HR]=0.47; 95% CI: 0.34-0.66; p<0.0001) compared to\ntrastuzumab emtansine (T-DM1) in patients with HER2 positive breast cancer\nwith residual invasive disease following neoadjuvant therapy. Enhertu\ndemonstrated a three-year IDFS rate of 92.4% (95% CI: 89.7-94.4) and 83.7%\nwith T-DM1 (95% CI: 80.2-86.7). Data also showed that Enhertu significantly\nreduced the risk of disease recurrence or death (disease-free survival [DFS])\nby 53% (HR=0.47; 95% CI: 0.34-0.66; p<0.0001) compared to T-DM1. Results\nshowed a three-year DFS rate of 92.3% (95% CI: 89.5-94.3) in the Enhertu arm\nand 83.5% with T-DM1 (95% CI: 79.9-86.4).\n\nBased on the results from DESTINY-Breast05, fam-trastuzumab deruxtecan-nxki\n(Enhertu) has been included in the NCCN Clinical Practice Guidelines in\nOncology (NCCN Guidelines(®)) as a Category 1 recommended treatment in the\nadjuvant setting for patients with HER2 positive early breast cancer with\nresidual disease following preoperative therapy and high risk of recurrence.\nSee NCCN Guidelines(®) for detailed recommendations.\n\n“HER2 positive breast cancer is an aggressive disease, and our goal is to\nreduce the risk of recurrence as early as possible to achieve the best\nlong‑term outcomes. The neoadjuvant setting offers the earliest opportunity\nto improve outcomes, while the adjuvant setting provides another important\nchance to prevent recurrence for patients with residual disease after\nsurgery,” said Shanu Modi, MD, medical oncologist, Memorial Sloan Kettering\nCancer Center and principal investigator for the DESTINY-Breast11 trial.\n“These two new indications in HER2 positive early breast cancer will evolve\nhow we treat patients in these settings and support trastuzumab deruxtecan as\na potential new standard of care in early-stage disease.”\n\n“Providing patients with early breast cancer more options to help prevent\nprogression to metastatic disease can lead to improved outcomes,” said\nVictoria Smart, Senior Vice President, Mission, Susan G. Komen. “Progression\nand recurrence remain among the most significant unmet needs for those\ndiagnosed with early breast cancer, and continued advances in treatment bring\nnew hope to patients and families facing this disease.”\n\nEnhertu is approved with Boxed WARNINGS for interstitial lung disease\n(ILD)/pneumonitis and Embryo-Fetal toxicity. The safety of Enhertu followed by\nTHP was evaluated in 320 patients with HER2 positive (IHC 3+ or ISH+) early\nbreast cancer who received at least one dose of Enhertu followed by THP in\nDESTINY-Breast11. The safety of Enhertu was evaluated in 806 patients with\nHER2 positive breast cancer with residual invasive disease following\nneoadjuvant therapy who received at least one dose of Enhertu in\nDESTINY-Breast05.\n\nIn DESTINY-Breast11, the most common adverse reactions (≥20%), including\nlaboratory abnormalities, were decreased hemoglobin, increased alanine\naminotransferase, increased aspartate aminotransferase, decreased white blood\ncell count, nausea, peripheral neuropathy, diarrhea, decreased neutrophil\ncount, alopecia, fatigue, decreased lymphocyte count, rash, musculoskeletal\npain, decreased blood potassium, constipation, vomiting, stomatitis and\ndecreased appetite. Serious adverse reactions occurred in 11% of patients\nreceiving Enhertu followed by THP, including COVID-19 (0.9%) and\nILD/pneumonitis (0.6%). Fatal adverse reactions occurred in 0.6% of patients,\nincluding ILD or pneumonitis and death not otherwise specified (one patient\neach).\n\nIn DESTINY-Breast05, the most common adverse reactions (≥20%), including\nlaboratory abnormalities, were decreased white blood cell count, decreased\nlymphocyte count, decreased neutrophil count, nausea, decreased hemoglobin,\nincreased aspartate aminotransferase, fatigue, increased alanine\naminotransferase, decreased platelet count, increased blood alkaline\nphosphatase, constipation, vomiting, decreased blood potassium, diarrhea,\nmusculoskeletal pain and decreased appetite. Serious adverse reactions\noccurred in 17% of patients receiving Enhertu. Serious adverse reactions in\n≥1% of patients who received Enhertu were ILD/pneumonitis, radiation\npneumonitis and decreased platelet count. Fatal adverse reactions occurred in\n0.4% of patients, including ILD/pneumonitis (two patients) and respiratory\ntract infection (one patient).\n\n“Enhertu has redefined the treatment of HER2 expressing breast cancer with\npractice-changing data across six breast cancer indications in seven years,”\nsaid Ken Keller, Global Head of Oncology Business, and President and CEO,\nDaiichi Sankyo, Inc. “Enhertu is now approved in the U.S. across both early\nand metastatic HER2 positive breast cancer, accomplishing what we set out to\nachieve a little over a decade ago for patients at the start of our\ncomprehensive clinical development program.”\n\n“HER2 positive early disease is considered highly curable, however, up to\none in four patients still experience disease recurrence, underscoring the\nneed for new options in this setting,” said Dave Fredrickson, Executive Vice\nPresident, Oncology Hematology Business Unit, AstraZeneca. “These approvals\nmark an important step forward, expanding the possibility of cure to more\npatients for the first time in many years and positioning Enhertu as a\nfoundational treatment in early breast cancer.”\n\nThese applications in the U.S. were reviewed under Project Orbis, which\nprovides a framework for concurrent submission and review of oncology\nmedicines among participating international partners. As part of Project\nOrbis, reviews for both DESTINY-Breast11 and DESTINY-Breast05 are ongoing in\nAustralia, Brazil, Canada, Israel, Singapore and the UK. Additional regulatory\nsubmissions for Enhertu based on DESTINY-Breast05 are under review in Japan,\nthe EU and Switzerland.\n\nDaiichi Sankyo and AstraZeneca are committed to ensuring that patients in the\nU.S. who are prescribed Enhertu can access the medication and receive\nnecessary financial support. Provider and patient support, reimbursement and\ndistribution for Enhertu in the U.S. will be accessible by visiting\nwww.Enhertu4U.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.Enhertu4U.com&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=www.Enhertu4U.com&index=5&md5=4d77cf9baae9dad5334d44c58d848689)\nor calling 1-833-Enhertu (1-833-364-3788).\n\nPlease visit www.Enhertu.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.Enhertu.com&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=www.Enhertu.com&index=6&md5=41d326893aafcdb5938ff5cd3cb0714b)\nfor full Prescribing Information\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Prescribing+Information&index=7&md5=d0e80bd9e967f189a2077b38a5251f39)\n, including Boxed WARNINGS, and Medication Guide\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu_Med%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Medication+Guide&index=8&md5=98fe38c312c6d8a029e2b8f42aa5ba27)\n.\n\nFinancial Considerations\n\nFollowing these approvals in the U.S., an amount of $155 million ($30 million\nfor the neoadjuvant approval and $125 million for the adjuvant approval) is\ndue from AstraZeneca to Daiichi Sankyo as milestone payments for these HER2\npositive early-stage breast cancer indications. Sales of Enhertu in the U.S.\nare recognized by Daiichi Sankyo. For further details on the financial\narrangements, please consult the collaboration agreement from March 2019\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.daiichisankyo.com%2Ffiles%2Fnews%2Fpressrelease%2Fpdf%2F006988%2F190329_886_E.pdf&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=March+2019&index=9&md5=cd66e870dbc650f80b5c3e013108dc90)\n.\n\nAbout DESTINY-Breast11\n\nDESTINY-Breast11\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast11&index=10&md5=d99bc722797ca8dc502ff5e308693636)\nis a global, multicenter, randomized, open-label, phase 3 trial evaluating the\nefficacy and safety of neoadjuvant Enhertu (5.4 mg/kg) monotherapy or Enhertu\nfollowed by THP compared to ddAC-THP in patients with high-risk HER2 positive\nearly-stage breast cancer.\n\nPatients were randomized 1:1:1 to receive either eight cycles of Enhertu\nmonotherapy; four cycles of Enhertu followed by four cycles of THP; or four\ncycles of ddAC followed by four cycles of THP.\n\nThe primary endpoint of DESTINY-Breast11 is rate of pCR (absence of invasive\ndisease in the breast and lymph nodes). Secondary endpoints include event-free\nsurvival, IDFS, overall survival (OS) and safety.\n\nDESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe,\nNorth America and South America. For more information about the trial, visit\nClinicalTrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=ClinicalTrials.gov&index=11&md5=2092f8c5bd0074c08a95cb028f297e48)\n.\n\nAbout DESTINY-Breast05\n\nDESTINY-Breast05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast05&index=12&md5=47c991ff099dfdc5aff780511a008722)\nis a global, multicenter, randomized, open-label, phase 3 trial evaluating the\nefficacy and safety of Enhertu (5.4 mg/kg) versus T-DM1 in patients with HER2\npositive early breast cancer with residual invasive disease in breast or\naxillary lymph nodes following neoadjuvant therapy and a high risk of\nrecurrence. High risk of recurrence was defined as presentation with\ninoperable cancer (prior to neoadjuvant therapy) or pathologically positive\naxillary lymph nodes following neoadjuvant therapy.\n\nThe primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS, which\nis defined as the time from randomization until first invasive local, axillary\nor distant recurrence or death from any cause. The key secondary endpoint is\ninvestigator-assessed DFS. Other secondary endpoints include OS, distant\nrecurrence-free interval, brain metastases-free interval and safety.\n\nDESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America,\nOceania and South America. For more information about the trial, visit\nClinicalTrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319%3Fterm%3DDestiny-Breast05%2520%26rank%3D1&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=ClinicalTrials.gov&index=13&md5=0eb4b0a5d8f839d2f4c4a67a2ac407a5)\n.\n\nAbout HER2 Positive Early Breast Cancer\n\nBreast cancer is the second most common cancer and one of the leading causes\nof cancer-related deaths worldwide.(1) More than two million breast cancer\ncases were diagnosed in 2022, with more than 665,000 deaths globally.(1) In\nthe U.S., approximately 320,000 cases of breast cancer are diagnosed annually\nwith more than 42,000 deaths.(2)\n\nHER2 is a tyrosine kinase receptor growth-promoting protein expressed on the\nsurface of many types of tumors, including breast cancer.(3) HER2 protein\noverexpression may occur as a result of HER2 gene amplification and is often\nassociated with aggressive disease and poor prognosis in breast cancer.(3) An\nestimated one in five cases of breast cancer is considered HER2 positive.(4)\nApproximately one in three patients with HER2 positive early-stage breast\ncancer is considered high-risk, meaning they are more likely to experience\ndisease recurrence and have a poor prognosis.(5)\n\nThere are two treatment settings for HER2 positive early breast cancer:\nneoadjuvant (before surgery) and adjuvant (after surgery). In the neoadjuvant\nsetting, the current standard of care varies across regions but generally\nconsists of combination chemotherapy regimens. In the U.S., the current\nstandard of care consists of a combination regimen of carboplatin,\ntrastuzumab, pertuzumab and a taxane.(6) For patients with HER2 positive early\nbreast cancer, reaching pCR with neoadjuvant treatment is an early indicator\nof improved long-term survival.(7) However, 39% to 66% of patients who receive\nneoadjuvant treatment do not reach pCR, putting them at increased risk of\ndisease recurrence.(8,9,10,11,12)\n\nIn the adjuvant setting, despite receiving additional treatment with current\nstandard of care for residual disease, some patients still experience invasive\ndisease or death.(13) Once patients are diagnosed with metastatic disease, the\nfive-year survival rate drops from nearly 90% to approximately 30%.(14)\nAdjuvant therapy represents a key opportunity to minimize the risk of\nrecurrence and prevent progression to metastatic disease for patients with\nresidual disease.(15,16)\n\nAbout Enhertu\n\nEnhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S.\nonly) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary\nDXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of\nDaiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific\nplatform. Enhertu consists of a HER2 monoclonal antibody attached to a number\nof topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via\ntetrapeptide-based cleavable linkers.\n\nEnhertu (5.4 mg/kg) is approved in the U.S. for the treatment of adult\npatients with HER2 positive breast cancer who have residual invasive disease\nfollowing neoadjuvant trastuzumab (with or without pertuzumab) and\ntaxane-based treatment based on the DESTINY-Breast05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast05&index=14&md5=df904e5e06902d4ac8f9ef796b2fea04)\ntrial.\n\nEnhertu (5.4 mg/kg) followed by THP is approved in China and the U.S. as a\nneoadjuvant treatment for adult patients with HER2 positive (IHC 3+ or ISH+)\nstage 2 or stage 3 breast cancer based on the results from the\nDESTINY-Breast11\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast11&index=15&md5=abd787c24f8fba06b452608f4d77b7ca)\ntrial. Continued approval in China for this indication may be contingent upon\nverification and description of clinical benefit in a confirmatory trial.\n\nEnhertu (5.4 mg/kg) in combination with pertuzumab is approved in Israel,\nSaudi Arabia, Switzerland, the United Arab Emirates and the U.S. as a\nfirst-line treatment for adult patients with unresectable or metastatic HER2\npositive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved\ntest, based on the results from the DESTINY-Breast09\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04784715&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast09&index=16&md5=dc5df0d7d52967872912e2a2efa39f54)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 95 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic HER2\npositive (IHC 3+ or ISH+) breast cancer who have received a prior\nanti-HER2-based regimen, either in the metastatic setting or in the\nneoadjuvant or adjuvant setting, and have developed disease recurrence during\nor within six months of completing therapy based on the results from the\nDESTINY-Breast03\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03529110&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast03&index=17&md5=91d15ddd82a63d089381bde489b8294a)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 95 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic HER2 low\n(IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic\ntherapy in the metastatic setting or developed disease recurrence during or\nwithin six months of completing adjuvant chemotherapy based on the results\nfrom the DESTINY-Breast04\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03734029&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast04&index=18&md5=bc43b6dabf8e808818c6db793a53a2ad)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 70 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic hormone\nreceptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ ISH-) or HER2 ultralow\n(IHC 0 with membrane staining) breast cancer, as determined by a locally or\nregionally approved test, that have progressed on one or more endocrine\ntherapies in the metastatic setting based on the results from the\nDESTINY-Breast06\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04494425&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast06&index=19&md5=c746966cc2ef2576cfd27b3fd5615244)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 75 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic NSCLC\nwhose tumors have activating HER2 (ERBB2) mutations, as detected by a locally\nor regionally approved test, and who have received a prior systemic therapy\nbased on the results from the DESTINY-Lung02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.clinicaltrials.gov%2Fstudy%2FNCT04644237&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Lung02&index=20&md5=e3d424101d77bce239e7fec7eb752c2e)\nand/or DESTINY-Lung05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05246514&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Lung05&index=21&md5=d7c184f10b1fe769ae6cafe9f73cf84e)\ntrials. Continued approval in China and the U.S. for this indication may be\ncontingent upon verification and description of clinical benefit in a\nconfirmatory trial.\n\nEnhertu (6.4 mg/kg) is approved in more than 90 countries/regions worldwide\nfor the treatment of adult patients with locally advanced or metastatic HER2\npositive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ)\nadenocarcinoma who have received a prior trastuzumab-based regimen based on\nthe results from the DESTINY-Gastric01\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03329690&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Gastric01&index=22&md5=23414000b2a7e5c89cfb6b2fe4c15a37)\n, DESTINY-Gastric02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04014075&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Gastric02&index=23&md5=0fc596ee2badbbfc2f1392826cd17762)\nand/or DESTINY-Gastric04\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04704934&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Gastric04&index=24&md5=fed7627e1dec7640e549c4120d2997fc)\ntrials.\n\nEnhertu (5.4 mg/kg) is approved in more than 15 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic HER2\npositive (IHC 3+) solid tumors who have received prior systemic treatment and\nhave no satisfactory alternative treatment options based on efficacy results\nfrom the DESTINY-PanTumor02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04482309&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-PanTumor02&index=25&md5=ece8281c92fc85799f8bec840c466119)\n, DESTINY-Lung01\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03505710&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Lung01&index=26&md5=ff9a39d0db158d01dd117b02519f3079)\n, DESTINY-CRC02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.clinicaltrials.gov%2Fstudy%2FNCT04744831&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-CRC02&index=27&md5=72652e435f6278d91454189f90022a26)\nand/or HERALD\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fjrct.mhlw.go.jp%2Fen-latest-detail%2FjRCT2080224635&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=HERALD&index=28&md5=4c034765ab2c21005789c7e656629356)\ntrials. Continued approval in the U.S. for this indication may be contingent\nupon verification and description of clinical benefit in a confirmatory trial.\n\nAbout the Enhertu Clinical Development Program\n\nA comprehensive global clinical development program is underway evaluating the\nefficacy and safety of Enhertu as a monotherapy or in combination or\nsequentially with other cancer medicines across multiple HER2 targetable\ncancers.\n\nAbout the Daiichi Sankyo and AstraZeneca Collaboration\n\nDaiichi Sankyo and AstraZeneca entered into a global collaboration to jointly\ndevelop and commercialize Enhertu in March 2019\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.daiichisankyo.com%2Fmedia%2Fpress_release%2Fdetail%2Findex_3199.html&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=March+2019&index=29&md5=636398fbbd230829e4ed8b36cd6e12e9)\nand Datroway(®) in July 2020\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.daiichisankyo.com%2Fmedia%2Fpress_release%2Fdetail%2Findex_3126.html&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=July+2020&index=30&md5=28a7ec3f001ccce5e804926fb4564f86)\n, except in Japan where Daiichi Sankyo maintains exclusive rights for each\nADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu\nand Datroway.\n\nEnhertu U.S. Indications and Important Safety Information\n\nIndications\n\nENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate\nindicated for:\n\n\n * HER2-Positive Early Breast Cancer\n\n\n* As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or\nISH+)\nStage II or III breast cancer, as determined by an FDA-authorized test\nfollowed by a taxane, trastuzumab, and pertuzumab (THP)\n\n * As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+)\nbreast cancer who have residual invasive disease following neoadjuvant\ntrastuzumab (with or without pertuzumab) and taxane-based treatment\n\n\n\n\n\n * HER2-Positive Metastatic Breast Cancer\n\n\n* In combination with pertuzumab as first-line treatment of adult patients\nwith\nunresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as\ndetermined by an FDA-authorized test\n\n * As monotherapy for the treatment of adult patients with unresectable or\nmetastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a\nprior anti-HER2-based regimen either in the metastatic setting, or, in the\nneoadjuvant or adjuvant setting and have developed disease recurrence during\nor within six months of completing therapy\n\n\n\n\n\n * HER2-Low and HER2-Ultralow Metastatic Breast Cancer\n\n\n* As monotherapy for the treatment of adult patients with unresectable or\nmetastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or\nHER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by\nan FDA-authorized test, that has progressed on one or more endocrine therapies\nin the metastatic setting\n\n * As monotherapy for the treatment of adult patients with unresectable or\nmetastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an\nFDA-authorized test, who have received a prior chemotherapy in the metastatic\nsetting or developed disease recurrence during or within 6 months of\ncompleting adjuvant chemotherapy\n\n\n\n\n\n * HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)\n\n\n* As monotherapy for the treatment of adult patients with unresectable or\nmetastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as\ndetected by an FDA-authorized test, and who have received a prior systemic\ntherapy\n\n\n\nThis indication is approved under accelerated approval based on objective\nresponse rate and duration of response. Continued approval for this indication\nmay be contingent upon verification and description of clinical benefit in a\nconfirmatory trial.\n\n\n\n\n\n * HER2-Positive Locally Advanced or Metastatic Gastric Cancer\n\n\n* As monotherapy for the treatment of adult patients with locally advanced or\nmetastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or\ngastroesophageal junction (GEJ) adenocarcinoma who have received a prior\ntrastuzumab-based regimen\n\n\n\n\n\n * HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors\n\n\n* As monotherapy for the treatment of adult patients with unresectable or\nmetastatic HER2-positive (IHC 3+) solid tumors who have received prior\nsystemic treatment and have no satisfactory alternative treatment options\n\n\n\nThis indication is approved under accelerated approval based on objective\nresponse rate and duration of response. Continued approval for this indication\nmay be contingent upon verification and description of clinical benefit in a\nconfirmatory trial.\n\n\n\n\nImportant Safety Information\n                                                                               \n WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY                  \n                                                                               \n * Interstitial lung disease (ILD) and pneumonitis, including severe,          \n life-threatening, and fatal cases, have been reported with ENHERTU. Monitor   \n for and promptly investigate signs and symptoms including cough, dyspnea,     \n fever, and other new or worsening respiratory symptoms. Permanently           \n discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis.   \n Advise patients of the risk and to immediately report symptoms.               \n \n*Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise    \n patients of these risks and the need for effective contraception.             \n                                                                               \n\n\nContraindications\n\nNone.\n\nWarnings and Precautions\n\nInterstitial Lung Disease / Pneumonitis\n\nSevere, life-threatening, or fatal interstitial lung disease (ILD), including\npneumonitis, can occur in patients treated with ENHERTU. A higher incidence of\nGrade 1 and 2 ILD/pneumonitis has been observed in patients with moderate\nrenal impairment. Advise patients to immediately report cough, dyspnea, fever,\nand/or any new or worsening respiratory symptoms. Monitor patients for signs\nand symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients\nwith suspected ILD by radiographic imaging. Consider consultation with a\npulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU\nuntil resolved to Grade 0, then if resolved in ≤28 days from date of onset,\nmaintain dose. If resolved in >28 days from date of onset, reduce dose 1\nlevel. Consider corticosteroid treatment as soon as ILD/pneumonitis is\nsuspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic\nILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU.\nPromptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis\nis suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue\nfor at least 14 days followed by gradual taper for at least 4 weeks. In the\nadjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule\nout radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis\nis suspected, consider interruption of ENHERTU for Grade 2 and permanently\ndiscontinue ENHERTU for Grade ≥3.\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nIn patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients.\nMedian time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes\ndue to ILD and/or pneumonitis occurred in 0.9% of patients treated with\nENHERTU.\n\nENHERTU in Combination with Pertuzumab\n\nIn patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab\n(N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0\nmonths (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis\noccurred in 0.5% of patients treated with ENHERTU in combination with\npertuzumab.\n\nENHERTU followed by THP\n\nIn patients treated with ENHERTU 5.4 mg/kg followed by THP in\nDESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset\nwas 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or\npneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nIn patients with locally advanced or metastatic HER2-positive gastric or GEJ\nadenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of\npatients. Median time to first onset was 2.8 months (range: 1.2 to 21).\n\nNeutropenia\n\nSevere neutropenia, including febrile neutropenia, can occur in patients\ntreated with ENHERTU. Monitor complete blood counts prior to initiation of\nENHERTU and prior to each dose, and as clinically indicated. For Grade 3\nneutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10(9)/L),\ninterrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For\nGrade 4 neutropenia (ANC <0.5 x 10(9)/L), interrupt ENHERTU until resolved\nto Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC\n<1.0 x 10(9)/L and temperature >38.3º C or a sustained temperature of\n≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce\ndose by 1 level.\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nIn patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was\nreported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased\nneutrophil count. Median time to first onset of decreased neutrophil count was\n22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.\n\nENHERTU in Combination with Pertuzumab\n\nIn patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab\n(N=431), decreased neutrophil count occurred in 79% of patients. Median time\nto first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3\nor 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of\npatients.\n\nENHERTU followed by THP\n\nIn patients treated with ENHERTU 5.4 mg/kg followed by THP in\nDESTINY-Breast11, a decrease in neutrophil count was reported in 58% of\npatients. Seventeen percent had Grade 3 or 4 decreased neutrophil count.\nMedian time to first onset of decreased neutrophil count was 42 days (range:\n11 to 165). Febrile neutropenia was reported in 0.9% of patients.\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nIn patients with locally advanced or metastatic HER2-positive gastric or GEJ\nadenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count\nwas reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased\nneutrophil count. Median time to first onset of decreased neutrophil count was\n16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of\npatients.\n\nLeft Ventricular Dysfunction\n\nPatients treated with ENHERTU may be at increased risk of developing left\nventricular dysfunction. Left ventricular dysfunction (LVD) has been observed\nwith anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection\nfraction (LVEF) prior to initiation of ENHERTU and at regular intervals during\ntreatment as clinically indicated. Manage LVD through treatment interruption.\nWhen LVEF is >45% and absolute decrease from baseline is 10-20%, continue\ntreatment with ENHERTU. When LVEF is 40-45% and absolute decrease from\nbaseline is <10%, continue treatment with ENHERTU and repeat LVEF\nassessment within 3 weeks. When LVEF is 40-45% and absolute decrease from\nbaseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3\nweeks. If LVEF has not recovered to within 10% from baseline, permanently\ndiscontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume\ntreatment with ENHERTU at the same dose. When LVEF is <40% or absolute\ndecrease from baseline is >20%, interrupt ENHERTU and repeat LVEF\nassessment within 3 weeks. If LVEF of <40% or absolute decrease from\nbaseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently\ndiscontinue ENHERTU in patients with symptomatic congestive heart failure.\nTreatment with ENHERTU has not been studied in patients with a history of\nclinically significant cardiac disease or LVEF <50% prior to initiation of\ntreatment.\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nIn patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of\npatients, of which 0.6% were Grade 3 or 4.\n\nENHERTU in Combination with Pertuzumab\n\nIn patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab\n(N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were\nGrade 3 or 4.\n\nENHERTU followed by THP\n\nIn patients treated with ENHERTU 5.4 mg/kg followed by THP in\nDESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were\nGrade 3.\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nIn patients with locally advanced or metastatic HER2-positive gastric or GEJ\nadenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of\nheart failure were reported; however, on echocardiography, 8% were found to\nhave asymptomatic Grade 2 decrease in LVEF.\n\nEmbryo-Fetal Toxicity\n\nENHERTU can cause fetal harm when administered to a pregnant woman. Advise\npatients of the potential risks to a fetus. Verify the pregnancy status of\nfemales of reproductive potential prior to the initiation of ENHERTU. Advise\nfemales of reproductive potential to use effective contraception during\ntreatment and for 7 months after the last dose of ENHERTU. Advise male\npatients with female partners of reproductive potential to use effective\ncontraception during treatment with ENHERTU and for 4 months after the last\ndose of ENHERTU.\n\nAdditional Dose Modifications\n\nThrombocytopenia\n\nFor Grade 3 thrombocytopenia (platelets <50 to 25 x 10(9)/L) interrupt\nENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4\nthrombocytopenia (platelets <25 x 10(9)/L) interrupt ENHERTU until resolved\nto Grade 1 or less, then reduce dose by 1 level.\n\nAdverse Reactions\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nThe pooled safety population reflects exposure to ENHERTU 5.4 mg/kg\nintravenously every 3 weeks in 2233 patients in Study DS8201-A-J101\n(NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03,\nDESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02,\nDESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed\nfor >6 months and 39% were exposed for >1 year. In this pooled safety\npopulation, the most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (73%), nausea (72%),\ndecreased hemoglobin (67%), decreased neutrophil count (65%), decreased\nlymphocyte count (60%), fatigue (55%), decreased platelet count (48%),\nincreased aspartate aminotransferase (46%), increased alanine aminotransferase\n(43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia\n(37%), constipation (32%), decreased blood potassium (32%), decreased appetite\n(31%), diarrhea (30%), and musculoskeletal pain (24%).\n\nENHERTU in Combination with Pertuzumab\n\nThe pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in\ncombination with pertuzumab intravenously every 3 weeks in 431 patients in\nDESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients,\n86% were exposed for >6 months and 73% were exposed for >1 year. In this\npooled safety population, the most common (≥20%) adverse reactions,\nincluding laboratory abnormalities, were decreased white blood cell count\n(86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea\n(74%), increased alanine aminotransferase (65%), diarrhea (64%), increased\naspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased\nplatelet count (55%), increased blood alkaline phosphatase (54%), decreased\nblood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper\nrespiratory tract infection (32%), constipation (31%), decreased appetite\n(31%), decreased weight (28%), musculoskeletal pain (23%), increased blood\nbilirubin (23%), and abdominal pain (22%).\n\nHER2-Positive Early Breast Cancer\n\nDESTINY-Breast11\n\nThe safety of ENHERTU followed by THP was evaluated in 320 patients with\nHER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1\ndose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was\nadministered by intravenous infusion once every three weeks for 4 cycles\nfollowed by THP for 4 cycles. The median duration of treatment was 5.6 months\n(range: 0.7 to 9.1) for patients who received ENHERTU followed by THP.\n\nSerious adverse reactions occurred in 11% of patients receiving ENHERTU\nfollowed by THP, including COVID-19 (0.9%) and ILD/pneumonitis (0.6%). Fatal\nadverse reactions occurred in 0.6% of patients, including ILD/pneumonitis and\ndeath not otherwise specified (1 patient each).\n\nIn patients treated with ENHERTU followed by THP, the permanent\ndiscontinuation of ENHERTU due to adverse reactions occurred in 1.3%, of which\nILD/pneumonitis accounted for 0.6%. Dose interruptions of ENHERTU due to\nadverse reactions occurred in 11% of patients. The most frequent adverse\nreactions (>2%) associated with dose interruption were decreased neutrophil\ncount and COVID-19. Dose reductions of ENHERTU occurred in 2.5% of patients\ntreated with ENHERTU.\n\nThe most common (≥20%) adverse reactions in patients treated with ENHERTU\nfollowed by THP, including laboratory abnormalities, were decreased hemoglobin\n(83%), increased alanine aminotransferase (79%), increased aspartate\naminotransferase (74%), decreased white blood cell count (67%), nausea (65%),\nperipheral neuropathy (59%), diarrhea (59%), decreased neutrophil count (58%),\nalopecia (48%), fatigue (41%), decreased lymphocyte count (40%), rash (31%),\nmusculoskeletal pain (30%), decreased blood potassium (29%), constipation\n(29%), vomiting (29%), stomatitis (23%), and decreased appetite (20%).\n\nDESTINY-Breast05\n\nThe safety of ENHERTU was evaluated in 806 patients with HER2-positive breast\ncancer with residual invasive disease following neoadjuvant HER2-targeted\ntherapy who then received at least one dose of ENHERTU 5.4 mg/kg. ENHERTU was\nadministered by intravenous infusion once every three weeks for 14 cycles. The\nmedian duration of treatment was 10 months (range: 0.7 to 16) for patients who\nreceived ENHERTU.\n\nSerious adverse reactions occurred in 17% of patients receiving ENHERTU.\nSerious adverse reactions in ≥1% of patients who received ENHERTU were\nILD/pneumonitis, radiation pneumonitis, pneumonia, and platelet count\ndecreased. Fatal adverse reactions occurred in 0.4% of patients including\nILD/pneumonitis (2 patients) and respiratory tract infection (1 patient).\n\nPermanent discontinuation of ENHERTU due to an adverse reaction occurred in\n18% of patients. The adverse reaction which resulted in permanent\ndiscontinuation of ENHERTU >2% included ILD/pneumonitis. Dose interruptions\nof ENHERTU due to an adverse reaction occurred in 50% of patients. Adverse\nreactions which required dosage interruptions in >2% included radiation\npneumonitis, neutrophil count decreased, COVID-19, white blood cell count\ndecreased, ILD/pneumonitis, platelet count decreased, upper respiratory tract\ninfection, fatigue, cough, and pyrexia. Dose reductions of ENHERTU due to an\nadverse reaction occurred in 26% of patients. Adverse reactions which required\ndose reductions in >2% of patients included nausea, fatigue, platelet count\ndecreased, ILD/pneumonitis, and neutrophil count decreased.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, in patients receiving ENHERTU were decreased white blood cell\ncount (80%), decreased lymphocyte count (72%), decreased neutrophil count\n(72%), nausea (71%), decreased hemoglobin (61%), increased aspartate\naminotransferase (60%), fatigue (54%), increased alanine aminotransferase\n(53%), decreased platelet count (46%), increased blood alkaline phosphatase\n(39%), constipation (32%), vomiting (31%), decreased blood potassium (27%),\ndiarrhea (23%), musculoskeletal pain (23%), and decreased appetite (20%).\n\nILD was reported in 17% of patients receiving ENHERTU, which included COVID-19\npneumonia, interstitial lung disease, lung opacity, organizing pneumonia,\npneumocystis jirovecii pneumonia, pneumonia, and pneumonitis which was\nadjudicated as ILD (irrespective of causality). Adjudicated drug-related ILD\nfor ENHERTU was 10% for all Grades and 0.9% for Grades 3 or 4.\n\nHER2-Positive Metastatic Breast Cancer\n\nDESTINY-Breast09\n\nThe safety of ENHERTU 5.4 mg/kg in combination with pertuzumab was evaluated\nin DESTINY-Breast09, a randomized, three-arm, multicenter study including 763\npatients with HER2-positive (IHC 3+ or ISH+) unresectable or metastatic breast\ncancer. Three hundred eighty-one patients received ENHERTU in combination with\npertuzumab and 382 patients received THP (taxane [docetaxel or paclitaxel],\ntrastuzumab, and pertuzumab). Among patients who received ENHERTU in\ncombination with pertuzumab, the median duration of treatment was 22 months\n(range: 0.3 months to 44.5 months).\n\nSerious adverse reactions occurred in 27% of patients receiving ENHERTU in\ncombination with pertuzumab. Serious adverse reactions in >1% of patients\nwere diarrhea, pneumonia, febrile neutropenia, hypokalemia, vomiting, ILD,\npulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred\nin 3.4% of patients including pneumonia (n=3), ILD (n=2), sepsis (n=2),\npulmonary embolism, septic shock, acute kidney injury, dyspnea, febrile\nneutropenia, and intestinal ischemia (1 patient each).\n\nENHERTU was discontinued for adverse reactions in 21% of patients. The most\nfrequent adverse reaction (>2%) associated with permanent discontinuation\nwas ILD/pneumonitis (6%). Dose interruptions due to adverse reactions occurred\nin 69% of patients. The most frequent adverse reactions (>2%) associated\nwith dose interruption were COVID-19, neutropenia, upper respiratory tract\ninfection, fatigue, anemia, hypokalemia, ILD/pneumonitis, thrombocytopenia,\npneumonia, diarrhea, transaminase increased, leukopenia, cough, pyrexia,\ndecreased appetite, and blood bilirubin increased. Dose reductions occurred in\n46% of patients treated with ENHERTU in combination with pertuzumab. The most\nfrequent adverse reactions (>2%) associated with dose reduction were\nfatigue, neutropenia, nausea, diarrhea, ILD/pneumonitis, thrombocytopenia,\nvomiting, transaminases increased, decreased weight, febrile neutropenia, and\nhypokalemia.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (87%), decreased\nhemoglobin (80%), decreased neutrophil count (78%), nausea (75%), increased\nalanine aminotransferase (66%), diarrhea (64%), increased aspartate\naminotransferase (62%), decreased lymphocyte count (62%), decreased platelet\ncount (56%), increased blood alkaline phosphatase (55%), decreased blood\npotassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper\nrespiratory tract infection (33%), constipation (33%), decreased appetite\n(32%), decreased weight (30%), COVID-19 (28%), musculoskeletal pain (24%),\nincreased blood bilirubin (23%), and abdominal pain (23%).\n\nDESTINY-Breast03\n\nThe safety of ENHERTU was evaluated in 257 patients with unresectable or\nmetastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU\n5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median\nduration of treatment was 14 months (range: 0.7 to 30) for patients who\nreceived ENHERTU.\n\nSerious adverse reactions occurred in 19% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nvomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due\nto adverse reactions occurred in 0.8% of patients including COVID-19 and\nsudden death (1 patient each).\n\nENHERTU was permanently discontinued in 14% of patients, of which\nILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions\noccurred in 44% of patients treated with ENHERTU. The most frequent adverse\nreactions (>2%) associated with dose interruption were neutropenia,\nleukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and\nILD/pneumonitis. Dose reductions occurred in 21% of patients treated with\nENHERTU. The most frequent adverse reactions (>2%) associated with dose\nreduction were nausea, neutropenia, and fatigue.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were nausea (76%), decreased white blood cell count (74%),\ndecreased neutrophil count (70%), increased aspartate aminotransferase (67%),\ndecreased hemoglobin (64%), decreased lymphocyte count (55%), increased\nalanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%),\nvomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%),\ndecreased blood potassium (35%), constipation (34%), musculoskeletal pain\n(31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory\ninfection (22%), abdominal pain (21%), increased blood bilirubin (20%), and\nstomatitis (20%).\n\nHER2-Low and HER2-Ultralow Metastatic Breast Cancer\n\nDESTINY-Breast06\n\nThe safety of ENHERTU was evaluated in 434 patients with unresectable or\nmetastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with\nmembrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously\nonce every 3 weeks in DESTINY-Breast06. The median duration of treatment was\n11 months (range: 0.4 to 39.6) for patients who received ENHERTU.\n\nSerious adverse reactions occurred in 20% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities\ndue to adverse reactions occurred in 2.8% of patients including ILD (0.7%);\nsepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis,\nneutropenic sepsis, peritonitis, cerebrovascular accident, general physical\nhealth deterioration (0.2% each).\n\nENHERTU was permanently discontinued in 14% of patients. The most frequent\nadverse reaction (>2%) associated with permanent discontinuation was\nILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48%\nof patients treated with ENHERTU. The most frequent adverse reactions (>2%)\nassociated with dose interruption were COVID-19, decreased neutrophil count,\nanemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose\nreductions occurred in 25% of patients treated with ENHERTU. The most frequent\nadverse reactions (>2%) associated with dose reduction were nausea,\nfatigue, decreased platelet count, and decreased neutrophil count.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (86%), decreased\nneutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased\nlymphocyte count (66%), fatigue (53%), decreased platelet count (48%),\nalopecia (48%), increased alanine aminotransferase (44%), increased blood\nalkaline phosphatase (43%), increased aspartate aminotransferase (41%),\ndecreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation\n(32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain\n(24%).\n\nDESTINY-Breast04\n\nThe safety of ENHERTU was evaluated in 371 patients with unresectable or\nmetastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU\n5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median\nduration of treatment was 8 months (range: 0.2 to 33) for patients who\nreceived ENHERTU.\n\nSerious adverse reactions occurred in 28% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia,\nfebrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities\ndue to adverse reactions occurred in 4% of patients including ILD/pneumonitis\n(3 patients); sepsis (2 patients); and ischemic colitis, disseminated\nintravascular coagulation, dyspnea, febrile neutropenia, general physical\nhealth deterioration, pleural effusion, and respiratory failure (1 patient\neach).\n\nENHERTU was permanently discontinued in 16% of patients, of which\nILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions\noccurred in 39% of patients treated with ENHERTU. The most frequent adverse\nreactions (>2%) associated with dose interruption were neutropenia,\nfatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased\ntransaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of\npatients treated with ENHERTU. The most frequent adverse reactions (>2%)\nassociated with dose reduction were fatigue, nausea, thrombocytopenia, and\nneutropenia.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were nausea (76%), decreased white blood cell count (70%),\ndecreased hemoglobin (64%), decreased neutrophil count (64%), decreased\nlymphocyte count (55%), fatigue (54%), decreased platelet count (44%),\nalopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%),\nincreased alanine aminotransferase (36%), constipation (34%), increased blood\nalkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain\n(32%), diarrhea (27%), and decreased blood potassium (25%).\n\nHER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)\n\nDESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg\n[n=50]); however, only the results for the recommended dose of 5.4 mg/kg\nintravenously every 3 weeks are described below due to increased toxicity\nobserved with the higher dose in patients with NSCLC, including\nILD/pneumonitis.\n\nThe safety of ENHERTU was evaluated in 101 patients with HER2-mutant\nunresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously\nonce every 3 weeks until disease progression or unacceptable toxicity in\nDESTINY‑Lung02. The median duration of treatment was 8 months (range: 0.7 to\n28) for patients who received ENHERTU.\n\nSerious adverse reactions occurred in 40% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nILD/pneumonitis, pleural effusion, thrombocytopenia, dyspnea, nausea,\npneumonia, vomiting, myocarditis, pulmonary embolism, and increased troponin\nI. Fatalities due to adverse reactions occurred in 3% of patients including\nILD/pneumonitis, cerebrovascular accident, and pneumococcal sepsis (1 patient\neach).\n\nENHERTU was permanently discontinued in 17% of patients. Adverse reactions\nwhich resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis,\npneumonia, blood bilirubin increased, hypokalemia, metastases to meninges, and\nmyocarditis. Dose interruptions of ENHERTU due to adverse reactions occurred\nin 50% of patients. Adverse reactions which required dose interruption\n(>2%) included neutropenia, COVID-19, ILD/pneumonitis, fatigue, anemia, and\npneumonia. Dose reductions due to an adverse reaction occurred in 20% of\npatients. The most frequent adverse reactions (>2%) associated with dose\nreduction were neutropenia, fatigue, and decreased appetite.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased hemoglobin (68%), nausea (67%), decreased white\nblood cell count (66%), decreased neutrophil count (59%), decreased lymphocyte\ncount (56%), increased aspartate aminotransferase (51%), decreased albumin\n(50%), decreased platelet count (49%), fatigue (48%), increased alanine\naminotransferase (41%), decreased appetite (41%), constipation (38%),\nincreased alkaline phosphatase (37%), vomiting (32%), decreased blood\npotassium (29%), diarrhea (24%), alopecia (22%), and musculoskeletal pain\n(21%).\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nThe safety of ENHERTU was evaluated in 187 patients with locally advanced or\nmetastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01.\nPatients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4\nmg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m(2) biweekly or\npaclitaxel (N=7) 80 mg/m(2) weekly for 3 weeks. The median duration of\ntreatment was 4.6 months (range: 0.7 to 22.3) for patients who received\nENHERTU.\n\nSerious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4\nmg/kg. Serious adverse reactions in >2% of patients who received ENHERTU\nwere decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic\njaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions\noccurred in 2.4% of patients: disseminated intravascular coagulation, large\nintestine perforation, and pneumonia occurred in 1 patient each (0.8%).\n\nENHERTU was permanently discontinued in 15% of patients, of which ILD\naccounted for 6%. Dose interruptions due to adverse reactions occurred in 62%\nof patients treated with ENHERTU. The most frequent adverse reactions (>2%)\nassociated with dose interruption were neutropenia, anemia, decreased\nappetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia,\nupper respiratory tract infection, diarrhea, and decreased blood potassium.\nDose reductions occurred in 32% of patients treated with ENHERTU. The most\nfrequent adverse reactions (>2%) associated with dose reduction were\nneutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased hemoglobin (75%), decreased white blood cell\ncount (74%), decreased neutrophil count (72%), decreased lymphocyte count\n(70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%),\nincreased aspartate aminotransferase (58%), fatigue (55%), increased blood\nalkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea\n(32%), decreased blood potassium (30%), vomiting (26%), constipation (24%),\nincreased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).\n\nHER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors\n\nThe safety of ENHERTU was evaluated in 347 adult patients with unresectable or\nmetastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg\nintravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02,\nDESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3\nmonths (range 0.7 to 30.2).\n\nSerious adverse reactions occurred in 34% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nsepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea,\npneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney\ninjury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions\noccurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest\n(0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1\npatient each (0.3%): acute kidney injury, cerebrovascular accident, general\nphysical health deterioration, pneumonia, and hemorrhagic shock.\n\nENHERTU was permanently discontinued in 15% of patients, of which\nILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions\noccurred in 48% of patients. The most frequent adverse reactions (>2%)\nassociated with dose interruption were decreased neutrophil count, anemia,\nCOVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose\nreductions occurred in 27% of patients treated with ENHERTU. The most frequent\nadverse reactions (>2%) associated with dose reduction were fatigue,\nnausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (75%), nausea (69%),\ndecreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%),\ndecreased lymphocyte count (58%), decreased platelet count (51%), increased\naspartate aminotransferase (45%), increased alanine aminotransferase (44%),\nincreased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite\n(34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%),\nconstipation (28%), decreased sodium (22%), stomatitis (20%), and upper\nrespiratory tract infection (20%).\n\nUse in Specific Populations\n\n\n * Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman.\nAdvise patients of the potential risks to a fetus. There are clinical\nconsiderations if ENHERTU is used in pregnant women, or if a patient becomes\npregnant within 7 months after the last dose of ENHERTU.\n\n * Lactation: There are no data regarding the presence of ENHERTU in human milk,\nthe effects on the breastfed child, or the effects on milk production. Because\nof the potential for serious adverse reactions in a breastfed child, advise\nwomen not to breastfeed during treatment with ENHERTU and for 7 months after\nthe last dose.\n\n * Females and Males of Reproductive Potential: Pregnancy testing: Verify\npregnancy status of females of reproductive potential prior to initiation of\nENHERTU. Contraception: Females: ENHERTU can cause fetal harm when\nadministered to a pregnant woman. Advise females of reproductive potential to\nuse effective contraception during treatment with ENHERTU and for 7 months\nafter the last dose. Males: Advise male patients with female partners of\nreproductive potential to use effective contraception during treatment with\nENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair\nmale reproductive function and fertility.\n\n * Pediatric Use: Safety and effectiveness of ENHERTU have not been established\nin pediatric patients.\n\n * Geriatric Use: ENHERTU as Monotherapy: Of the 2233 patients treated with\nENHERTU 5.4 mg/kg, 28% were ≥65 years and 6% were ≥75 years. No overall\ndifferences in efficacy within clinical studies were observed between patients\n≥65 years compared to younger patients. There was a higher incidence of\nGrade 3-4 adverse reactions observed in patients aged ≥65 years (56%) as\ncompared to younger patients (49%). Of the 125 patients with HER2-positive\nlocally advanced or metastatic gastric or GEJ adenocarcinoma treated with\nENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were\n≥75 years. No overall differences in efficacy or safety were observed\nbetween patients ≥65 years of age compared to younger patients. ENHERTU in\nCombination with Pertuzumab: In patients with HER2-positive unresectable or\nmetastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with\npertuzumab (N=431), 17% were ≥65 years and 3% were ≥75 years. No overall\ndifferences in efficacy or safety were observed between patients ≥65 years\ncompared to younger patients. ENHERTU followed by THP: Of the 320 patients\nwith HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed\nby THP, 12% were ≥65 years and 1.6% were ≥75 years. No overall differences\nin efficacy were observed between patients ≥65 years compared to younger\npatients. There was a higher incidence of Grade 3-4 adverse reactions observed\nin patients ≥65 years (38%) as compared to younger patients (30%).\n\n * Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been\nobserved in patients with moderate renal impairment. Monitor patients with\nmoderate renal impairment more frequently. The recommended dosage of ENHERTU\nhas not been established for patients with severe renal impairment (CLcr\n<30 mL/min).\n\n * Hepatic Impairment: In patients with moderate hepatic impairment, due to\npotentially increased exposure, monitor for increased adverse reactions\nrelated to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU\nhas not been established for patients with severe hepatic impairment (total\nbilirubin >3 times ULN and any AST).\n\nTo report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at\n1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.\n\nPlease see accompanying full Prescribing Information\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Prescribing+Information&index=31&md5=588fdaf74ae51b1738e50aad0f7ea490)\n, including Boxed WARNINGS, and Medication Guide\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu_Med%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Medication+Guide&index=32&md5=2f06e990c95a94bcda7dbeb7ee6254d7)\n.\n\nAbout the ADC Portfolio of Daiichi Sankyo\n\nThe Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical\ndevelopment crafted from ADC technology discovered in-house by Daiichi Sankyo.\n\nThe DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in\nclinical development where each ADC is comprised of a monoclonal antibody\nattached to a number of topoisomerase I inhibitor payloads (an exatecan\nderivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs\ninclude Enhertu and Datroway, which are being jointly developed and\ncommercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd),\nraludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are\nbeing jointly developed and commercialized globally with Merck & Co., Inc,\nRahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo.\n\nAn additional ADC being developed by Daiichi Sankyo is DS3610, which consists\nof an antibody attached to a novel payload that acts as an agonist of STING.\n\nIfinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939,\nDS3610 and DS3790 are investigational medicines that have not been approved\nfor any indication in any country. Safety and efficacy have not been\nestablished.\n\nAbout Daiichi Sankyo\n\nDaiichi Sankyo (TSE: 4568) is a global healthcare company committed to\nbecoming a trusted healthcare innovator, transforming the lives of people\nthrough its strength in science and technology. The company discovers and\ndevelops new standards of care to address diverse medical needs to fulfill its\npurpose of contributing to the enrichment of quality of life around the world.\nWith a strategic focus on oncology, Daiichi Sankyo is advancing an\nindustry-leading antibody drug conjugate portfolio along with identifying new\nbreakthrough generating technologies to deliver practice-changing medicines to\npatients, healthcare professionals and society. For more information, please\nvisit www.daiichisankyo.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.daiichisankyo.com&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=www.daiichisankyo.com&index=33&md5=54666999315767a4dae9a3b90dbea9f8)\n.\n\nDisclosure: Dr. Modi provides consulting and advisory services to Daiichi\nSankyo (and AstraZeneca).\n\nReferences:\n\n(1) World Health Organization. Breast Fact Sheet\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fgco.iarc.who.int%2Fmedia%2Fglobocan%2Ffactsheets%2Fcancers%2F20-breast-fact-sheet.pdf&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Breast+Fact+Sheet&index=34&md5=bf4746e49b88d05946cb44149354e636)\n. Accessed May 2026.\n\n(2) Siegel RL, et al. CA Cancer J Clin\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Facsjournals.onlinelibrary.wiley.com%2Fdoi%2F10.3322%2Fcaac.70043&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=CA+Cancer+J+Clin&index=35&md5=ad6addf8deacf17bee3f3a5342d010a8)\n. 2026;76(1):e70043.\n\n(3) Cheng X. Genes\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.mdpi.com%2F2073-4425%2F15%2F7%2F903&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Genes&index=36&md5=8096b2528f23799c376479b8e2316dba)\n(Basel). 2024;15(7):903.\n\n(4) Tarantino P, et al. Ann Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252823%252900693-2%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Ann+Oncol&index=37&md5=7769963882eba6f971a338c95c8be419)\n. 2023;34(8):645-659.\n\n(5) Mahtani R, et al. Cancers\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.mdpi.com%2F2072-6694%2F17%2F11%2F1848&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Cancers&index=38&md5=50356515713ae436eec5e84f252f6581)\n(Basel). 2025;17(11):1848.\n\n(6) Wang J, et al. Breast Cancer\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdoi.org%2F10.2147%2FBCTT.S432526&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Breast+Cancer&index=39&md5=e9f962557f2118d8170ebd594bbfcc8c)\n. 2023;15:721-730.\n\n(7) Spring LM, et al. Clin Cancer Res\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Faacrjournals.org%2Fclincancerres%2Farticle-abstract%2F26%2F12%2F2838%2F82378%2FPathologic-Complete-Response-after-Neoadjuvant%3FredirectedFrom%3Dfulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Clin+Cancer+Res&index=40&md5=e3d0a6fef017e3a60e142c543cdf837c)\n. 2020;26(12):2838-2848.\n\n(8) Schneeweiss A, et al. Ann Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252819%252936929-7%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Ann+Oncol&index=41&md5=788b05ddcdfcec47b1156b0579859393)\n. 2013;24(9):2278-2284.\n\n(9) Swain SM, et al. Ann Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252819%252935495-X%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Ann+Oncol&index=42&md5=c3bbb27dc3da1b6b264f5cdd91117aa0)\n. 2018;29(3):646-653.\n\n(10) Huober J, et al. J Clin Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fascopubs.org%2Fdoi%2F10.1200%2FJCO.21.02772%3Furl_ver%3DZ39.88-2003%26rfr_id%3Dori%3Arid%3Acrossref.org%26rfr_dat%3Dcr_pub%2520%25200pubmed&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=J+Clin+Oncol&index=43&md5=b6c432008c65d749e586d9fa4b89310f)\n. 2022;40(25):2946-2956.\n\n(11) Masuda N, et al. Breast Cancer Res Treat\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs10549-020-05524-6&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Breast+Cancer+Res+Treat&index=44&md5=f6d9ebca3d55350cc703aac67cfb9cf9)\n. 2020;180(1):135-146.\n\n(12) Gao HF, et al. Presented at ASCO Annual Meeting 2025.\n\n(13) Geyer CE, et al. N Engl J Med\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nejm.org%2Fdoi%2F10.1056%2FNEJMoa2406070%3Furl_ver%3DZ39.88-2003%26rfr_id%3Dori%3Arid%3Acrossref.org%26rfr_dat%3Dcr_pub%2520%25200pubmed&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=N+Engl+J+Med&index=45&md5=2f836eaa7f5e8445c87746ba75749b37)\n. 2025;392:249-257.\n\n(14) National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer.\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fseer.cancer.gov%2Fstatfacts%2Fhtml%2Fbreast.html&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=SEER+Cancer+Stat+Facts%3A+Female+Breast+Cancer.&index=46&md5=c08af5fac7a2f41f96d92c62cf42a261)\nAccessed May 2026.\n\n(15) von Minckwitz G, et al. N Engl J Med\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F30516102%2F&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=N+Engl+J+Med&index=47&md5=f7e78a6b3c8a5acf1cfcfcc09afd9afe)\n. 2019;380(7):617-628.\n\n(16) Zaborowski AM and Wong SM. BJS.\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Facademic.oup.com%2Fbjs%2Farticle%2F110%2F7%2F765%2F7145840&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=BJS.&index=48&md5=3e9dabbeea043f0382ad9164dca260fe)\n2023;110(7):765-772.\n\nPP-US-ENB-5118-1\n\n05/26\n\n\n\nView source version on businesswire.com:\nhttps://www.businesswire.com/news/home/20260513022601/en/\n(https://www.businesswire.com/news/home/20260513022601/en/)\n\nMEDIA CONTACTS: \n\nGlobal: \n\nJennifer Brennan\n\njennifer.brennan@daiichisankyo.com \n(mailto:jennifer.brennan@daiichisankyo.com) \n+1 908 900 3183 (mobile)\n\n\n\nJapan: \n\nDS-PR_jp@daiichisankyo.com \n(mailto:DS-PR_jp@daiichisankyo.com) \n\n\nINVESTOR RELATIONS CONTACT: \n\nDaiichiSankyoIR_jp@daiichisankyo.com\n(mailto:DaiichiSankyoIR_jp@daiichisankyo.com)\n\n\nCopyright Business Wire 2026","article_body_html":"","raw_payload":{"data":{"id":"nBw4Zt4QQa","title":"Enhertu® Approved in the U.S. for Two New Indications for Patients with HER2 Positive Early Breast Cancer","author":"Business Wire","ticker":"4568","created":"2026-05-15T22:31:00.078Z","tickers":["4568"],"exchange":"TSE Tokyo","article_body":"Enhertu(®) Approved in the U.S. for Two New Indications for Patients with\nHER2 Positive Early Breast Cancer\n\n\n * Approved for use before surgery based on DESTINY-Breast11 phase 3 trial or\nfollowing surgery based on DESTINY-Breast05 phase 3 trial\n\n * Two new indications bring Daiichi Sankyo and AstraZeneca’s Enhertu into\ncurative-intent setting, reinforcing its role across stages of HER2 positive\nbreast cancer\n\n * Enhertu now approved for nine indications with six across both early and\nmetastatic HER2 positive breast cancer\n\nEnhertu(®) (fam-trastuzumab deruxtecan-nxki) has been approved by the U.S.\nFood and Drug Administration (FDA) for two new breast cancer indications in\nthe neoadjuvant and adjuvant settings of patients with HER2 positive early\nbreast cancer.\n\nIn the neoadjuvant setting, Enhertu followed by a taxane, trastuzumab and\npertuzumab (THP) has been approved for the treatment of adult patients with\nHER2 positive stage 2 or stage 3 breast cancer. In the adjuvant setting,\nEnhertu has been approved for the treatment of adult patients with HER2\npositive breast cancer who have residual invasive disease following\nneoadjuvant trastuzumab (with or without pertuzumab) and taxane-based\ntreatment.\n\nEnhertu is a specifically engineered HER2 directed DXd antibody drug conjugate\n(ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and\ncommercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/NYSE: AZN).\n\nThe neoadjuvant approval was based on results from the DESTINY-Breast11\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast11&index=1&md5=9998b6f4b4475479b61fe7eddaec6776)\nphase 3 trial published in Annals of Oncology\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252825%252904968-3%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Annals+of+Oncology&index=2&md5=5ddfb4de9c9bc01f6979dce342e9488a)\nand the adjuvant approval was based on the results from the DESTINY-Breast05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast05&index=3&md5=90e7d01504612a8f7dfcefbe8377119a)\nphase 3 trial published in The New England Journal of Medicine\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nejm.org%2F&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=The+New+England+Journal+of+Medicine&index=4&md5=eda21a0ee9da940d0b458b4b894a5b12)\n.( )Data from both trials were presented at the 2025 European Society for\nMedical Oncology (ESMO) Congress.\n\nIn DESTINY-Breast11, Enhertu followed by THP demonstrated a statistically\nsignificant and clinically meaningful improvement in the pathologic complete\nresponse (pCR) rate compared to dose-dense doxorubicin and cyclophosphamide\nfollowed by THP (ddAC-THP) in patients with high-risk, locally advanced HER2\npositive early-stage breast cancer. Pathologic complete response is defined as\nno evidence of invasive cancer cells in the removed breast tissue and lymph\nnodes following treatment. The pCR rate with Enhertu followed by THP was 67.3%\ncompared with 56.3% with ddAC-THP, representing a difference of 11.2% (95%\nconfidence interval [CI]: 3.9-18.3; p=0.003).\n\nIn DESTINY-Breast05, Enhertu significantly reduced the risk of invasive\ndisease recurrence or death (invasive disease-free survival [IDFS]) by 53%\n(hazard ratio [HR]=0.47; 95% CI: 0.34-0.66; p<0.0001) compared to\ntrastuzumab emtansine (T-DM1) in patients with HER2 positive breast cancer\nwith residual invasive disease following neoadjuvant therapy. Enhertu\ndemonstrated a three-year IDFS rate of 92.4% (95% CI: 89.7-94.4) and 83.7%\nwith T-DM1 (95% CI: 80.2-86.7). Data also showed that Enhertu significantly\nreduced the risk of disease recurrence or death (disease-free survival [DFS])\nby 53% (HR=0.47; 95% CI: 0.34-0.66; p<0.0001) compared to T-DM1. Results\nshowed a three-year DFS rate of 92.3% (95% CI: 89.5-94.3) in the Enhertu arm\nand 83.5% with T-DM1 (95% CI: 79.9-86.4).\n\nBased on the results from DESTINY-Breast05, fam-trastuzumab deruxtecan-nxki\n(Enhertu) has been included in the NCCN Clinical Practice Guidelines in\nOncology (NCCN Guidelines(®)) as a Category 1 recommended treatment in the\nadjuvant setting for patients with HER2 positive early breast cancer with\nresidual disease following preoperative therapy and high risk of recurrence.\nSee NCCN Guidelines(®) for detailed recommendations.\n\n“HER2 positive breast cancer is an aggressive disease, and our goal is to\nreduce the risk of recurrence as early as possible to achieve the best\nlong‑term outcomes. The neoadjuvant setting offers the earliest opportunity\nto improve outcomes, while the adjuvant setting provides another important\nchance to prevent recurrence for patients with residual disease after\nsurgery,” said Shanu Modi, MD, medical oncologist, Memorial Sloan Kettering\nCancer Center and principal investigator for the DESTINY-Breast11 trial.\n“These two new indications in HER2 positive early breast cancer will evolve\nhow we treat patients in these settings and support trastuzumab deruxtecan as\na potential new standard of care in early-stage disease.”\n\n“Providing patients with early breast cancer more options to help prevent\nprogression to metastatic disease can lead to improved outcomes,” said\nVictoria Smart, Senior Vice President, Mission, Susan G. Komen. “Progression\nand recurrence remain among the most significant unmet needs for those\ndiagnosed with early breast cancer, and continued advances in treatment bring\nnew hope to patients and families facing this disease.”\n\nEnhertu is approved with Boxed WARNINGS for interstitial lung disease\n(ILD)/pneumonitis and Embryo-Fetal toxicity. The safety of Enhertu followed by\nTHP was evaluated in 320 patients with HER2 positive (IHC 3+ or ISH+) early\nbreast cancer who received at least one dose of Enhertu followed by THP in\nDESTINY-Breast11. The safety of Enhertu was evaluated in 806 patients with\nHER2 positive breast cancer with residual invasive disease following\nneoadjuvant therapy who received at least one dose of Enhertu in\nDESTINY-Breast05.\n\nIn DESTINY-Breast11, the most common adverse reactions (≥20%), including\nlaboratory abnormalities, were decreased hemoglobin, increased alanine\naminotransferase, increased aspartate aminotransferase, decreased white blood\ncell count, nausea, peripheral neuropathy, diarrhea, decreased neutrophil\ncount, alopecia, fatigue, decreased lymphocyte count, rash, musculoskeletal\npain, decreased blood potassium, constipation, vomiting, stomatitis and\ndecreased appetite. Serious adverse reactions occurred in 11% of patients\nreceiving Enhertu followed by THP, including COVID-19 (0.9%) and\nILD/pneumonitis (0.6%). Fatal adverse reactions occurred in 0.6% of patients,\nincluding ILD or pneumonitis and death not otherwise specified (one patient\neach).\n\nIn DESTINY-Breast05, the most common adverse reactions (≥20%), including\nlaboratory abnormalities, were decreased white blood cell count, decreased\nlymphocyte count, decreased neutrophil count, nausea, decreased hemoglobin,\nincreased aspartate aminotransferase, fatigue, increased alanine\naminotransferase, decreased platelet count, increased blood alkaline\nphosphatase, constipation, vomiting, decreased blood potassium, diarrhea,\nmusculoskeletal pain and decreased appetite. Serious adverse reactions\noccurred in 17% of patients receiving Enhertu. Serious adverse reactions in\n≥1% of patients who received Enhertu were ILD/pneumonitis, radiation\npneumonitis and decreased platelet count. Fatal adverse reactions occurred in\n0.4% of patients, including ILD/pneumonitis (two patients) and respiratory\ntract infection (one patient).\n\n“Enhertu has redefined the treatment of HER2 expressing breast cancer with\npractice-changing data across six breast cancer indications in seven years,”\nsaid Ken Keller, Global Head of Oncology Business, and President and CEO,\nDaiichi Sankyo, Inc. “Enhertu is now approved in the U.S. across both early\nand metastatic HER2 positive breast cancer, accomplishing what we set out to\nachieve a little over a decade ago for patients at the start of our\ncomprehensive clinical development program.”\n\n“HER2 positive early disease is considered highly curable, however, up to\none in four patients still experience disease recurrence, underscoring the\nneed for new options in this setting,” said Dave Fredrickson, Executive Vice\nPresident, Oncology Hematology Business Unit, AstraZeneca. “These approvals\nmark an important step forward, expanding the possibility of cure to more\npatients for the first time in many years and positioning Enhertu as a\nfoundational treatment in early breast cancer.”\n\nThese applications in the U.S. were reviewed under Project Orbis, which\nprovides a framework for concurrent submission and review of oncology\nmedicines among participating international partners. As part of Project\nOrbis, reviews for both DESTINY-Breast11 and DESTINY-Breast05 are ongoing in\nAustralia, Brazil, Canada, Israel, Singapore and the UK. Additional regulatory\nsubmissions for Enhertu based on DESTINY-Breast05 are under review in Japan,\nthe EU and Switzerland.\n\nDaiichi Sankyo and AstraZeneca are committed to ensuring that patients in the\nU.S. who are prescribed Enhertu can access the medication and receive\nnecessary financial support. Provider and patient support, reimbursement and\ndistribution for Enhertu in the U.S. will be accessible by visiting\nwww.Enhertu4U.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.Enhertu4U.com&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=www.Enhertu4U.com&index=5&md5=4d77cf9baae9dad5334d44c58d848689)\nor calling 1-833-Enhertu (1-833-364-3788).\n\nPlease visit www.Enhertu.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.Enhertu.com&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=www.Enhertu.com&index=6&md5=41d326893aafcdb5938ff5cd3cb0714b)\nfor full Prescribing Information\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Prescribing+Information&index=7&md5=d0e80bd9e967f189a2077b38a5251f39)\n, including Boxed WARNINGS, and Medication Guide\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu_Med%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Medication+Guide&index=8&md5=98fe38c312c6d8a029e2b8f42aa5ba27)\n.\n\nFinancial Considerations\n\nFollowing these approvals in the U.S., an amount of $155 million ($30 million\nfor the neoadjuvant approval and $125 million for the adjuvant approval) is\ndue from AstraZeneca to Daiichi Sankyo as milestone payments for these HER2\npositive early-stage breast cancer indications. Sales of Enhertu in the U.S.\nare recognized by Daiichi Sankyo. For further details on the financial\narrangements, please consult the collaboration agreement from March 2019\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.daiichisankyo.com%2Ffiles%2Fnews%2Fpressrelease%2Fpdf%2F006988%2F190329_886_E.pdf&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=March+2019&index=9&md5=cd66e870dbc650f80b5c3e013108dc90)\n.\n\nAbout DESTINY-Breast11\n\nDESTINY-Breast11\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast11&index=10&md5=d99bc722797ca8dc502ff5e308693636)\nis a global, multicenter, randomized, open-label, phase 3 trial evaluating the\nefficacy and safety of neoadjuvant Enhertu (5.4 mg/kg) monotherapy or Enhertu\nfollowed by THP compared to ddAC-THP in patients with high-risk HER2 positive\nearly-stage breast cancer.\n\nPatients were randomized 1:1:1 to receive either eight cycles of Enhertu\nmonotherapy; four cycles of Enhertu followed by four cycles of THP; or four\ncycles of ddAC followed by four cycles of THP.\n\nThe primary endpoint of DESTINY-Breast11 is rate of pCR (absence of invasive\ndisease in the breast and lymph nodes). Secondary endpoints include event-free\nsurvival, IDFS, overall survival (OS) and safety.\n\nDESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe,\nNorth America and South America. For more information about the trial, visit\nClinicalTrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=ClinicalTrials.gov&index=11&md5=2092f8c5bd0074c08a95cb028f297e48)\n.\n\nAbout DESTINY-Breast05\n\nDESTINY-Breast05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast05&index=12&md5=47c991ff099dfdc5aff780511a008722)\nis a global, multicenter, randomized, open-label, phase 3 trial evaluating the\nefficacy and safety of Enhertu (5.4 mg/kg) versus T-DM1 in patients with HER2\npositive early breast cancer with residual invasive disease in breast or\naxillary lymph nodes following neoadjuvant therapy and a high risk of\nrecurrence. High risk of recurrence was defined as presentation with\ninoperable cancer (prior to neoadjuvant therapy) or pathologically positive\naxillary lymph nodes following neoadjuvant therapy.\n\nThe primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS, which\nis defined as the time from randomization until first invasive local, axillary\nor distant recurrence or death from any cause. The key secondary endpoint is\ninvestigator-assessed DFS. Other secondary endpoints include OS, distant\nrecurrence-free interval, brain metastases-free interval and safety.\n\nDESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America,\nOceania and South America. For more information about the trial, visit\nClinicalTrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319%3Fterm%3DDestiny-Breast05%2520%26rank%3D1&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=ClinicalTrials.gov&index=13&md5=0eb4b0a5d8f839d2f4c4a67a2ac407a5)\n.\n\nAbout HER2 Positive Early Breast Cancer\n\nBreast cancer is the second most common cancer and one of the leading causes\nof cancer-related deaths worldwide.(1) More than two million breast cancer\ncases were diagnosed in 2022, with more than 665,000 deaths globally.(1) In\nthe U.S., approximately 320,000 cases of breast cancer are diagnosed annually\nwith more than 42,000 deaths.(2)\n\nHER2 is a tyrosine kinase receptor growth-promoting protein expressed on the\nsurface of many types of tumors, including breast cancer.(3) HER2 protein\noverexpression may occur as a result of HER2 gene amplification and is often\nassociated with aggressive disease and poor prognosis in breast cancer.(3) An\nestimated one in five cases of breast cancer is considered HER2 positive.(4)\nApproximately one in three patients with HER2 positive early-stage breast\ncancer is considered high-risk, meaning they are more likely to experience\ndisease recurrence and have a poor prognosis.(5)\n\nThere are two treatment settings for HER2 positive early breast cancer:\nneoadjuvant (before surgery) and adjuvant (after surgery). In the neoadjuvant\nsetting, the current standard of care varies across regions but generally\nconsists of combination chemotherapy regimens. In the U.S., the current\nstandard of care consists of a combination regimen of carboplatin,\ntrastuzumab, pertuzumab and a taxane.(6) For patients with HER2 positive early\nbreast cancer, reaching pCR with neoadjuvant treatment is an early indicator\nof improved long-term survival.(7) However, 39% to 66% of patients who receive\nneoadjuvant treatment do not reach pCR, putting them at increased risk of\ndisease recurrence.(8,9,10,11,12)\n\nIn the adjuvant setting, despite receiving additional treatment with current\nstandard of care for residual disease, some patients still experience invasive\ndisease or death.(13) Once patients are diagnosed with metastatic disease, the\nfive-year survival rate drops from nearly 90% to approximately 30%.(14)\nAdjuvant therapy represents a key opportunity to minimize the risk of\nrecurrence and prevent progression to metastatic disease for patients with\nresidual disease.(15,16)\n\nAbout Enhertu\n\nEnhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S.\nonly) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary\nDXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of\nDaiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific\nplatform. Enhertu consists of a HER2 monoclonal antibody attached to a number\nof topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via\ntetrapeptide-based cleavable linkers.\n\nEnhertu (5.4 mg/kg) is approved in the U.S. for the treatment of adult\npatients with HER2 positive breast cancer who have residual invasive disease\nfollowing neoadjuvant trastuzumab (with or without pertuzumab) and\ntaxane-based treatment based on the DESTINY-Breast05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04622319&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast05&index=14&md5=df904e5e06902d4ac8f9ef796b2fea04)\ntrial.\n\nEnhertu (5.4 mg/kg) followed by THP is approved in China and the U.S. as a\nneoadjuvant treatment for adult patients with HER2 positive (IHC 3+ or ISH+)\nstage 2 or stage 3 breast cancer based on the results from the\nDESTINY-Breast11\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05113251&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast11&index=15&md5=abd787c24f8fba06b452608f4d77b7ca)\ntrial. Continued approval in China for this indication may be contingent upon\nverification and description of clinical benefit in a confirmatory trial.\n\nEnhertu (5.4 mg/kg) in combination with pertuzumab is approved in Israel,\nSaudi Arabia, Switzerland, the United Arab Emirates and the U.S. as a\nfirst-line treatment for adult patients with unresectable or metastatic HER2\npositive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved\ntest, based on the results from the DESTINY-Breast09\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04784715&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast09&index=16&md5=dc5df0d7d52967872912e2a2efa39f54)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 95 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic HER2\npositive (IHC 3+ or ISH+) breast cancer who have received a prior\nanti-HER2-based regimen, either in the metastatic setting or in the\nneoadjuvant or adjuvant setting, and have developed disease recurrence during\nor within six months of completing therapy based on the results from the\nDESTINY-Breast03\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03529110&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast03&index=17&md5=91d15ddd82a63d089381bde489b8294a)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 95 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic HER2 low\n(IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic\ntherapy in the metastatic setting or developed disease recurrence during or\nwithin six months of completing adjuvant chemotherapy based on the results\nfrom the DESTINY-Breast04\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03734029&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast04&index=18&md5=bc43b6dabf8e808818c6db793a53a2ad)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 70 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic hormone\nreceptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ ISH-) or HER2 ultralow\n(IHC 0 with membrane staining) breast cancer, as determined by a locally or\nregionally approved test, that have progressed on one or more endocrine\ntherapies in the metastatic setting based on the results from the\nDESTINY-Breast06\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04494425&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Breast06&index=19&md5=c746966cc2ef2576cfd27b3fd5615244)\ntrial.\n\nEnhertu (5.4 mg/kg) is approved in more than 75 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic NSCLC\nwhose tumors have activating HER2 (ERBB2) mutations, as detected by a locally\nor regionally approved test, and who have received a prior systemic therapy\nbased on the results from the DESTINY-Lung02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.clinicaltrials.gov%2Fstudy%2FNCT04644237&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Lung02&index=20&md5=e3d424101d77bce239e7fec7eb752c2e)\nand/or DESTINY-Lung05\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT05246514&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Lung05&index=21&md5=d7c184f10b1fe769ae6cafe9f73cf84e)\ntrials. Continued approval in China and the U.S. for this indication may be\ncontingent upon verification and description of clinical benefit in a\nconfirmatory trial.\n\nEnhertu (6.4 mg/kg) is approved in more than 90 countries/regions worldwide\nfor the treatment of adult patients with locally advanced or metastatic HER2\npositive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ)\nadenocarcinoma who have received a prior trastuzumab-based regimen based on\nthe results from the DESTINY-Gastric01\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03329690&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Gastric01&index=22&md5=23414000b2a7e5c89cfb6b2fe4c15a37)\n, DESTINY-Gastric02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04014075&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Gastric02&index=23&md5=0fc596ee2badbbfc2f1392826cd17762)\nand/or DESTINY-Gastric04\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04704934&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Gastric04&index=24&md5=fed7627e1dec7640e549c4120d2997fc)\ntrials.\n\nEnhertu (5.4 mg/kg) is approved in more than 15 countries/regions worldwide\nfor the treatment of adult patients with unresectable or metastatic HER2\npositive (IHC 3+) solid tumors who have received prior systemic treatment and\nhave no satisfactory alternative treatment options based on efficacy results\nfrom the DESTINY-PanTumor02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04482309&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-PanTumor02&index=25&md5=ece8281c92fc85799f8bec840c466119)\n, DESTINY-Lung01\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT03505710&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-Lung01&index=26&md5=ff9a39d0db158d01dd117b02519f3079)\n, DESTINY-CRC02\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.clinicaltrials.gov%2Fstudy%2FNCT04744831&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=DESTINY-CRC02&index=27&md5=72652e435f6278d91454189f90022a26)\nand/or HERALD\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fjrct.mhlw.go.jp%2Fen-latest-detail%2FjRCT2080224635&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=HERALD&index=28&md5=4c034765ab2c21005789c7e656629356)\ntrials. Continued approval in the U.S. for this indication may be contingent\nupon verification and description of clinical benefit in a confirmatory trial.\n\nAbout the Enhertu Clinical Development Program\n\nA comprehensive global clinical development program is underway evaluating the\nefficacy and safety of Enhertu as a monotherapy or in combination or\nsequentially with other cancer medicines across multiple HER2 targetable\ncancers.\n\nAbout the Daiichi Sankyo and AstraZeneca Collaboration\n\nDaiichi Sankyo and AstraZeneca entered into a global collaboration to jointly\ndevelop and commercialize Enhertu in March 2019\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.daiichisankyo.com%2Fmedia%2Fpress_release%2Fdetail%2Findex_3199.html&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=March+2019&index=29&md5=636398fbbd230829e4ed8b36cd6e12e9)\nand Datroway(®) in July 2020\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.daiichisankyo.com%2Fmedia%2Fpress_release%2Fdetail%2Findex_3126.html&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=July+2020&index=30&md5=28a7ec3f001ccce5e804926fb4564f86)\n, except in Japan where Daiichi Sankyo maintains exclusive rights for each\nADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu\nand Datroway.\n\nEnhertu U.S. Indications and Important Safety Information\n\nIndications\n\nENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate\nindicated for:\n\n\n * HER2-Positive Early Breast Cancer\n\n\n* As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or\nISH+)\nStage II or III breast cancer, as determined by an FDA-authorized test\nfollowed by a taxane, trastuzumab, and pertuzumab (THP)\n\n * As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+)\nbreast cancer who have residual invasive disease following neoadjuvant\ntrastuzumab (with or without pertuzumab) and taxane-based treatment\n\n\n\n\n\n * HER2-Positive Metastatic Breast Cancer\n\n\n* In combination with pertuzumab as first-line treatment of adult patients\nwith\nunresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as\ndetermined by an FDA-authorized test\n\n * As monotherapy for the treatment of adult patients with unresectable or\nmetastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a\nprior anti-HER2-based regimen either in the metastatic setting, or, in the\nneoadjuvant or adjuvant setting and have developed disease recurrence during\nor within six months of completing therapy\n\n\n\n\n\n * HER2-Low and HER2-Ultralow Metastatic Breast Cancer\n\n\n* As monotherapy for the treatment of adult patients with unresectable or\nmetastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or\nHER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by\nan FDA-authorized test, that has progressed on one or more endocrine therapies\nin the metastatic setting\n\n * As monotherapy for the treatment of adult patients with unresectable or\nmetastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an\nFDA-authorized test, who have received a prior chemotherapy in the metastatic\nsetting or developed disease recurrence during or within 6 months of\ncompleting adjuvant chemotherapy\n\n\n\n\n\n * HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)\n\n\n* As monotherapy for the treatment of adult patients with unresectable or\nmetastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as\ndetected by an FDA-authorized test, and who have received a prior systemic\ntherapy\n\n\n\nThis indication is approved under accelerated approval based on objective\nresponse rate and duration of response. Continued approval for this indication\nmay be contingent upon verification and description of clinical benefit in a\nconfirmatory trial.\n\n\n\n\n\n * HER2-Positive Locally Advanced or Metastatic Gastric Cancer\n\n\n* As monotherapy for the treatment of adult patients with locally advanced or\nmetastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or\ngastroesophageal junction (GEJ) adenocarcinoma who have received a prior\ntrastuzumab-based regimen\n\n\n\n\n\n * HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors\n\n\n* As monotherapy for the treatment of adult patients with unresectable or\nmetastatic HER2-positive (IHC 3+) solid tumors who have received prior\nsystemic treatment and have no satisfactory alternative treatment options\n\n\n\nThis indication is approved under accelerated approval based on objective\nresponse rate and duration of response. Continued approval for this indication\nmay be contingent upon verification and description of clinical benefit in a\nconfirmatory trial.\n\n\n\n\nImportant Safety Information\n                                                                               \n WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY                  \n                                                                               \n * Interstitial lung disease (ILD) and pneumonitis, including severe,          \n life-threatening, and fatal cases, have been reported with ENHERTU. Monitor   \n for and promptly investigate signs and symptoms including cough, dyspnea,     \n fever, and other new or worsening respiratory symptoms. Permanently           \n discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis.   \n Advise patients of the risk and to immediately report symptoms.               \n \n*Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise    \n patients of these risks and the need for effective contraception.             \n                                                                               \n\n\nContraindications\n\nNone.\n\nWarnings and Precautions\n\nInterstitial Lung Disease / Pneumonitis\n\nSevere, life-threatening, or fatal interstitial lung disease (ILD), including\npneumonitis, can occur in patients treated with ENHERTU. A higher incidence of\nGrade 1 and 2 ILD/pneumonitis has been observed in patients with moderate\nrenal impairment. Advise patients to immediately report cough, dyspnea, fever,\nand/or any new or worsening respiratory symptoms. Monitor patients for signs\nand symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients\nwith suspected ILD by radiographic imaging. Consider consultation with a\npulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU\nuntil resolved to Grade 0, then if resolved in ≤28 days from date of onset,\nmaintain dose. If resolved in >28 days from date of onset, reduce dose 1\nlevel. Consider corticosteroid treatment as soon as ILD/pneumonitis is\nsuspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic\nILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU.\nPromptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis\nis suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue\nfor at least 14 days followed by gradual taper for at least 4 weeks. In the\nadjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule\nout radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis\nis suspected, consider interruption of ENHERTU for Grade 2 and permanently\ndiscontinue ENHERTU for Grade ≥3.\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nIn patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients.\nMedian time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes\ndue to ILD and/or pneumonitis occurred in 0.9% of patients treated with\nENHERTU.\n\nENHERTU in Combination with Pertuzumab\n\nIn patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab\n(N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0\nmonths (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis\noccurred in 0.5% of patients treated with ENHERTU in combination with\npertuzumab.\n\nENHERTU followed by THP\n\nIn patients treated with ENHERTU 5.4 mg/kg followed by THP in\nDESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset\nwas 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or\npneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nIn patients with locally advanced or metastatic HER2-positive gastric or GEJ\nadenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of\npatients. Median time to first onset was 2.8 months (range: 1.2 to 21).\n\nNeutropenia\n\nSevere neutropenia, including febrile neutropenia, can occur in patients\ntreated with ENHERTU. Monitor complete blood counts prior to initiation of\nENHERTU and prior to each dose, and as clinically indicated. For Grade 3\nneutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10(9)/L),\ninterrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For\nGrade 4 neutropenia (ANC <0.5 x 10(9)/L), interrupt ENHERTU until resolved\nto Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC\n<1.0 x 10(9)/L and temperature >38.3º C or a sustained temperature of\n≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce\ndose by 1 level.\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nIn patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was\nreported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased\nneutrophil count. Median time to first onset of decreased neutrophil count was\n22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.\n\nENHERTU in Combination with Pertuzumab\n\nIn patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab\n(N=431), decreased neutrophil count occurred in 79% of patients. Median time\nto first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3\nor 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of\npatients.\n\nENHERTU followed by THP\n\nIn patients treated with ENHERTU 5.4 mg/kg followed by THP in\nDESTINY-Breast11, a decrease in neutrophil count was reported in 58% of\npatients. Seventeen percent had Grade 3 or 4 decreased neutrophil count.\nMedian time to first onset of decreased neutrophil count was 42 days (range:\n11 to 165). Febrile neutropenia was reported in 0.9% of patients.\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nIn patients with locally advanced or metastatic HER2-positive gastric or GEJ\nadenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count\nwas reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased\nneutrophil count. Median time to first onset of decreased neutrophil count was\n16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of\npatients.\n\nLeft Ventricular Dysfunction\n\nPatients treated with ENHERTU may be at increased risk of developing left\nventricular dysfunction. Left ventricular dysfunction (LVD) has been observed\nwith anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection\nfraction (LVEF) prior to initiation of ENHERTU and at regular intervals during\ntreatment as clinically indicated. Manage LVD through treatment interruption.\nWhen LVEF is >45% and absolute decrease from baseline is 10-20%, continue\ntreatment with ENHERTU. When LVEF is 40-45% and absolute decrease from\nbaseline is <10%, continue treatment with ENHERTU and repeat LVEF\nassessment within 3 weeks. When LVEF is 40-45% and absolute decrease from\nbaseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3\nweeks. If LVEF has not recovered to within 10% from baseline, permanently\ndiscontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume\ntreatment with ENHERTU at the same dose. When LVEF is <40% or absolute\ndecrease from baseline is >20%, interrupt ENHERTU and repeat LVEF\nassessment within 3 weeks. If LVEF of <40% or absolute decrease from\nbaseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently\ndiscontinue ENHERTU in patients with symptomatic congestive heart failure.\nTreatment with ENHERTU has not been studied in patients with a history of\nclinically significant cardiac disease or LVEF <50% prior to initiation of\ntreatment.\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nIn patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of\npatients, of which 0.6% were Grade 3 or 4.\n\nENHERTU in Combination with Pertuzumab\n\nIn patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab\n(N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were\nGrade 3 or 4.\n\nENHERTU followed by THP\n\nIn patients treated with ENHERTU 5.4 mg/kg followed by THP in\nDESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were\nGrade 3.\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nIn patients with locally advanced or metastatic HER2-positive gastric or GEJ\nadenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of\nheart failure were reported; however, on echocardiography, 8% were found to\nhave asymptomatic Grade 2 decrease in LVEF.\n\nEmbryo-Fetal Toxicity\n\nENHERTU can cause fetal harm when administered to a pregnant woman. Advise\npatients of the potential risks to a fetus. Verify the pregnancy status of\nfemales of reproductive potential prior to the initiation of ENHERTU. Advise\nfemales of reproductive potential to use effective contraception during\ntreatment and for 7 months after the last dose of ENHERTU. Advise male\npatients with female partners of reproductive potential to use effective\ncontraception during treatment with ENHERTU and for 4 months after the last\ndose of ENHERTU.\n\nAdditional Dose Modifications\n\nThrombocytopenia\n\nFor Grade 3 thrombocytopenia (platelets <50 to 25 x 10(9)/L) interrupt\nENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4\nthrombocytopenia (platelets <25 x 10(9)/L) interrupt ENHERTU until resolved\nto Grade 1 or less, then reduce dose by 1 level.\n\nAdverse Reactions\n\nHER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC,\nand Solid Tumors (Including IHC 3+) (5.4 mg/kg)\n\nENHERTU as Monotherapy\n\nThe pooled safety population reflects exposure to ENHERTU 5.4 mg/kg\nintravenously every 3 weeks in 2233 patients in Study DS8201-A-J101\n(NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03,\nDESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02,\nDESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed\nfor >6 months and 39% were exposed for >1 year. In this pooled safety\npopulation, the most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (73%), nausea (72%),\ndecreased hemoglobin (67%), decreased neutrophil count (65%), decreased\nlymphocyte count (60%), fatigue (55%), decreased platelet count (48%),\nincreased aspartate aminotransferase (46%), increased alanine aminotransferase\n(43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia\n(37%), constipation (32%), decreased blood potassium (32%), decreased appetite\n(31%), diarrhea (30%), and musculoskeletal pain (24%).\n\nENHERTU in Combination with Pertuzumab\n\nThe pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in\ncombination with pertuzumab intravenously every 3 weeks in 431 patients in\nDESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients,\n86% were exposed for >6 months and 73% were exposed for >1 year. In this\npooled safety population, the most common (≥20%) adverse reactions,\nincluding laboratory abnormalities, were decreased white blood cell count\n(86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea\n(74%), increased alanine aminotransferase (65%), diarrhea (64%), increased\naspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased\nplatelet count (55%), increased blood alkaline phosphatase (54%), decreased\nblood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper\nrespiratory tract infection (32%), constipation (31%), decreased appetite\n(31%), decreased weight (28%), musculoskeletal pain (23%), increased blood\nbilirubin (23%), and abdominal pain (22%).\n\nHER2-Positive Early Breast Cancer\n\nDESTINY-Breast11\n\nThe safety of ENHERTU followed by THP was evaluated in 320 patients with\nHER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1\ndose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was\nadministered by intravenous infusion once every three weeks for 4 cycles\nfollowed by THP for 4 cycles. The median duration of treatment was 5.6 months\n(range: 0.7 to 9.1) for patients who received ENHERTU followed by THP.\n\nSerious adverse reactions occurred in 11% of patients receiving ENHERTU\nfollowed by THP, including COVID-19 (0.9%) and ILD/pneumonitis (0.6%). Fatal\nadverse reactions occurred in 0.6% of patients, including ILD/pneumonitis and\ndeath not otherwise specified (1 patient each).\n\nIn patients treated with ENHERTU followed by THP, the permanent\ndiscontinuation of ENHERTU due to adverse reactions occurred in 1.3%, of which\nILD/pneumonitis accounted for 0.6%. Dose interruptions of ENHERTU due to\nadverse reactions occurred in 11% of patients. The most frequent adverse\nreactions (>2%) associated with dose interruption were decreased neutrophil\ncount and COVID-19. Dose reductions of ENHERTU occurred in 2.5% of patients\ntreated with ENHERTU.\n\nThe most common (≥20%) adverse reactions in patients treated with ENHERTU\nfollowed by THP, including laboratory abnormalities, were decreased hemoglobin\n(83%), increased alanine aminotransferase (79%), increased aspartate\naminotransferase (74%), decreased white blood cell count (67%), nausea (65%),\nperipheral neuropathy (59%), diarrhea (59%), decreased neutrophil count (58%),\nalopecia (48%), fatigue (41%), decreased lymphocyte count (40%), rash (31%),\nmusculoskeletal pain (30%), decreased blood potassium (29%), constipation\n(29%), vomiting (29%), stomatitis (23%), and decreased appetite (20%).\n\nDESTINY-Breast05\n\nThe safety of ENHERTU was evaluated in 806 patients with HER2-positive breast\ncancer with residual invasive disease following neoadjuvant HER2-targeted\ntherapy who then received at least one dose of ENHERTU 5.4 mg/kg. ENHERTU was\nadministered by intravenous infusion once every three weeks for 14 cycles. The\nmedian duration of treatment was 10 months (range: 0.7 to 16) for patients who\nreceived ENHERTU.\n\nSerious adverse reactions occurred in 17% of patients receiving ENHERTU.\nSerious adverse reactions in ≥1% of patients who received ENHERTU were\nILD/pneumonitis, radiation pneumonitis, pneumonia, and platelet count\ndecreased. Fatal adverse reactions occurred in 0.4% of patients including\nILD/pneumonitis (2 patients) and respiratory tract infection (1 patient).\n\nPermanent discontinuation of ENHERTU due to an adverse reaction occurred in\n18% of patients. The adverse reaction which resulted in permanent\ndiscontinuation of ENHERTU >2% included ILD/pneumonitis. Dose interruptions\nof ENHERTU due to an adverse reaction occurred in 50% of patients. Adverse\nreactions which required dosage interruptions in >2% included radiation\npneumonitis, neutrophil count decreased, COVID-19, white blood cell count\ndecreased, ILD/pneumonitis, platelet count decreased, upper respiratory tract\ninfection, fatigue, cough, and pyrexia. Dose reductions of ENHERTU due to an\nadverse reaction occurred in 26% of patients. Adverse reactions which required\ndose reductions in >2% of patients included nausea, fatigue, platelet count\ndecreased, ILD/pneumonitis, and neutrophil count decreased.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, in patients receiving ENHERTU were decreased white blood cell\ncount (80%), decreased lymphocyte count (72%), decreased neutrophil count\n(72%), nausea (71%), decreased hemoglobin (61%), increased aspartate\naminotransferase (60%), fatigue (54%), increased alanine aminotransferase\n(53%), decreased platelet count (46%), increased blood alkaline phosphatase\n(39%), constipation (32%), vomiting (31%), decreased blood potassium (27%),\ndiarrhea (23%), musculoskeletal pain (23%), and decreased appetite (20%).\n\nILD was reported in 17% of patients receiving ENHERTU, which included COVID-19\npneumonia, interstitial lung disease, lung opacity, organizing pneumonia,\npneumocystis jirovecii pneumonia, pneumonia, and pneumonitis which was\nadjudicated as ILD (irrespective of causality). Adjudicated drug-related ILD\nfor ENHERTU was 10% for all Grades and 0.9% for Grades 3 or 4.\n\nHER2-Positive Metastatic Breast Cancer\n\nDESTINY-Breast09\n\nThe safety of ENHERTU 5.4 mg/kg in combination with pertuzumab was evaluated\nin DESTINY-Breast09, a randomized, three-arm, multicenter study including 763\npatients with HER2-positive (IHC 3+ or ISH+) unresectable or metastatic breast\ncancer. Three hundred eighty-one patients received ENHERTU in combination with\npertuzumab and 382 patients received THP (taxane [docetaxel or paclitaxel],\ntrastuzumab, and pertuzumab). Among patients who received ENHERTU in\ncombination with pertuzumab, the median duration of treatment was 22 months\n(range: 0.3 months to 44.5 months).\n\nSerious adverse reactions occurred in 27% of patients receiving ENHERTU in\ncombination with pertuzumab. Serious adverse reactions in >1% of patients\nwere diarrhea, pneumonia, febrile neutropenia, hypokalemia, vomiting, ILD,\npulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred\nin 3.4% of patients including pneumonia (n=3), ILD (n=2), sepsis (n=2),\npulmonary embolism, septic shock, acute kidney injury, dyspnea, febrile\nneutropenia, and intestinal ischemia (1 patient each).\n\nENHERTU was discontinued for adverse reactions in 21% of patients. The most\nfrequent adverse reaction (>2%) associated with permanent discontinuation\nwas ILD/pneumonitis (6%). Dose interruptions due to adverse reactions occurred\nin 69% of patients. The most frequent adverse reactions (>2%) associated\nwith dose interruption were COVID-19, neutropenia, upper respiratory tract\ninfection, fatigue, anemia, hypokalemia, ILD/pneumonitis, thrombocytopenia,\npneumonia, diarrhea, transaminase increased, leukopenia, cough, pyrexia,\ndecreased appetite, and blood bilirubin increased. Dose reductions occurred in\n46% of patients treated with ENHERTU in combination with pertuzumab. The most\nfrequent adverse reactions (>2%) associated with dose reduction were\nfatigue, neutropenia, nausea, diarrhea, ILD/pneumonitis, thrombocytopenia,\nvomiting, transaminases increased, decreased weight, febrile neutropenia, and\nhypokalemia.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (87%), decreased\nhemoglobin (80%), decreased neutrophil count (78%), nausea (75%), increased\nalanine aminotransferase (66%), diarrhea (64%), increased aspartate\naminotransferase (62%), decreased lymphocyte count (62%), decreased platelet\ncount (56%), increased blood alkaline phosphatase (55%), decreased blood\npotassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper\nrespiratory tract infection (33%), constipation (33%), decreased appetite\n(32%), decreased weight (30%), COVID-19 (28%), musculoskeletal pain (24%),\nincreased blood bilirubin (23%), and abdominal pain (23%).\n\nDESTINY-Breast03\n\nThe safety of ENHERTU was evaluated in 257 patients with unresectable or\nmetastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU\n5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median\nduration of treatment was 14 months (range: 0.7 to 30) for patients who\nreceived ENHERTU.\n\nSerious adverse reactions occurred in 19% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nvomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due\nto adverse reactions occurred in 0.8% of patients including COVID-19 and\nsudden death (1 patient each).\n\nENHERTU was permanently discontinued in 14% of patients, of which\nILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions\noccurred in 44% of patients treated with ENHERTU. The most frequent adverse\nreactions (>2%) associated with dose interruption were neutropenia,\nleukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and\nILD/pneumonitis. Dose reductions occurred in 21% of patients treated with\nENHERTU. The most frequent adverse reactions (>2%) associated with dose\nreduction were nausea, neutropenia, and fatigue.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were nausea (76%), decreased white blood cell count (74%),\ndecreased neutrophil count (70%), increased aspartate aminotransferase (67%),\ndecreased hemoglobin (64%), decreased lymphocyte count (55%), increased\nalanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%),\nvomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%),\ndecreased blood potassium (35%), constipation (34%), musculoskeletal pain\n(31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory\ninfection (22%), abdominal pain (21%), increased blood bilirubin (20%), and\nstomatitis (20%).\n\nHER2-Low and HER2-Ultralow Metastatic Breast Cancer\n\nDESTINY-Breast06\n\nThe safety of ENHERTU was evaluated in 434 patients with unresectable or\nmetastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with\nmembrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously\nonce every 3 weeks in DESTINY-Breast06. The median duration of treatment was\n11 months (range: 0.4 to 39.6) for patients who received ENHERTU.\n\nSerious adverse reactions occurred in 20% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities\ndue to adverse reactions occurred in 2.8% of patients including ILD (0.7%);\nsepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis,\nneutropenic sepsis, peritonitis, cerebrovascular accident, general physical\nhealth deterioration (0.2% each).\n\nENHERTU was permanently discontinued in 14% of patients. The most frequent\nadverse reaction (>2%) associated with permanent discontinuation was\nILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48%\nof patients treated with ENHERTU. The most frequent adverse reactions (>2%)\nassociated with dose interruption were COVID-19, decreased neutrophil count,\nanemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose\nreductions occurred in 25% of patients treated with ENHERTU. The most frequent\nadverse reactions (>2%) associated with dose reduction were nausea,\nfatigue, decreased platelet count, and decreased neutrophil count.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (86%), decreased\nneutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased\nlymphocyte count (66%), fatigue (53%), decreased platelet count (48%),\nalopecia (48%), increased alanine aminotransferase (44%), increased blood\nalkaline phosphatase (43%), increased aspartate aminotransferase (41%),\ndecreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation\n(32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain\n(24%).\n\nDESTINY-Breast04\n\nThe safety of ENHERTU was evaluated in 371 patients with unresectable or\nmetastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU\n5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median\nduration of treatment was 8 months (range: 0.2 to 33) for patients who\nreceived ENHERTU.\n\nSerious adverse reactions occurred in 28% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia,\nfebrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities\ndue to adverse reactions occurred in 4% of patients including ILD/pneumonitis\n(3 patients); sepsis (2 patients); and ischemic colitis, disseminated\nintravascular coagulation, dyspnea, febrile neutropenia, general physical\nhealth deterioration, pleural effusion, and respiratory failure (1 patient\neach).\n\nENHERTU was permanently discontinued in 16% of patients, of which\nILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions\noccurred in 39% of patients treated with ENHERTU. The most frequent adverse\nreactions (>2%) associated with dose interruption were neutropenia,\nfatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased\ntransaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of\npatients treated with ENHERTU. The most frequent adverse reactions (>2%)\nassociated with dose reduction were fatigue, nausea, thrombocytopenia, and\nneutropenia.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were nausea (76%), decreased white blood cell count (70%),\ndecreased hemoglobin (64%), decreased neutrophil count (64%), decreased\nlymphocyte count (55%), fatigue (54%), decreased platelet count (44%),\nalopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%),\nincreased alanine aminotransferase (36%), constipation (34%), increased blood\nalkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain\n(32%), diarrhea (27%), and decreased blood potassium (25%).\n\nHER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)\n\nDESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg\n[n=50]); however, only the results for the recommended dose of 5.4 mg/kg\nintravenously every 3 weeks are described below due to increased toxicity\nobserved with the higher dose in patients with NSCLC, including\nILD/pneumonitis.\n\nThe safety of ENHERTU was evaluated in 101 patients with HER2-mutant\nunresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously\nonce every 3 weeks until disease progression or unacceptable toxicity in\nDESTINY‑Lung02. The median duration of treatment was 8 months (range: 0.7 to\n28) for patients who received ENHERTU.\n\nSerious adverse reactions occurred in 40% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nILD/pneumonitis, pleural effusion, thrombocytopenia, dyspnea, nausea,\npneumonia, vomiting, myocarditis, pulmonary embolism, and increased troponin\nI. Fatalities due to adverse reactions occurred in 3% of patients including\nILD/pneumonitis, cerebrovascular accident, and pneumococcal sepsis (1 patient\neach).\n\nENHERTU was permanently discontinued in 17% of patients. Adverse reactions\nwhich resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis,\npneumonia, blood bilirubin increased, hypokalemia, metastases to meninges, and\nmyocarditis. Dose interruptions of ENHERTU due to adverse reactions occurred\nin 50% of patients. Adverse reactions which required dose interruption\n(>2%) included neutropenia, COVID-19, ILD/pneumonitis, fatigue, anemia, and\npneumonia. Dose reductions due to an adverse reaction occurred in 20% of\npatients. The most frequent adverse reactions (>2%) associated with dose\nreduction were neutropenia, fatigue, and decreased appetite.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased hemoglobin (68%), nausea (67%), decreased white\nblood cell count (66%), decreased neutrophil count (59%), decreased lymphocyte\ncount (56%), increased aspartate aminotransferase (51%), decreased albumin\n(50%), decreased platelet count (49%), fatigue (48%), increased alanine\naminotransferase (41%), decreased appetite (41%), constipation (38%),\nincreased alkaline phosphatase (37%), vomiting (32%), decreased blood\npotassium (29%), diarrhea (24%), alopecia (22%), and musculoskeletal pain\n(21%).\n\nHER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)\n\nThe safety of ENHERTU was evaluated in 187 patients with locally advanced or\nmetastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01.\nPatients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4\nmg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m(2) biweekly or\npaclitaxel (N=7) 80 mg/m(2) weekly for 3 weeks. The median duration of\ntreatment was 4.6 months (range: 0.7 to 22.3) for patients who received\nENHERTU.\n\nSerious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4\nmg/kg. Serious adverse reactions in >2% of patients who received ENHERTU\nwere decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic\njaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions\noccurred in 2.4% of patients: disseminated intravascular coagulation, large\nintestine perforation, and pneumonia occurred in 1 patient each (0.8%).\n\nENHERTU was permanently discontinued in 15% of patients, of which ILD\naccounted for 6%. Dose interruptions due to adverse reactions occurred in 62%\nof patients treated with ENHERTU. The most frequent adverse reactions (>2%)\nassociated with dose interruption were neutropenia, anemia, decreased\nappetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia,\nupper respiratory tract infection, diarrhea, and decreased blood potassium.\nDose reductions occurred in 32% of patients treated with ENHERTU. The most\nfrequent adverse reactions (>2%) associated with dose reduction were\nneutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased hemoglobin (75%), decreased white blood cell\ncount (74%), decreased neutrophil count (72%), decreased lymphocyte count\n(70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%),\nincreased aspartate aminotransferase (58%), fatigue (55%), increased blood\nalkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea\n(32%), decreased blood potassium (30%), vomiting (26%), constipation (24%),\nincreased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).\n\nHER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors\n\nThe safety of ENHERTU was evaluated in 347 adult patients with unresectable or\nmetastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg\nintravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02,\nDESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3\nmonths (range 0.7 to 30.2).\n\nSerious adverse reactions occurred in 34% of patients receiving ENHERTU.\nSerious adverse reactions in >1% of patients who received ENHERTU were\nsepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea,\npneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney\ninjury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions\noccurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest\n(0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1\npatient each (0.3%): acute kidney injury, cerebrovascular accident, general\nphysical health deterioration, pneumonia, and hemorrhagic shock.\n\nENHERTU was permanently discontinued in 15% of patients, of which\nILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions\noccurred in 48% of patients. The most frequent adverse reactions (>2%)\nassociated with dose interruption were decreased neutrophil count, anemia,\nCOVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose\nreductions occurred in 27% of patients treated with ENHERTU. The most frequent\nadverse reactions (>2%) associated with dose reduction were fatigue,\nnausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea.\n\nThe most common (≥20%) adverse reactions, including laboratory\nabnormalities, were decreased white blood cell count (75%), nausea (69%),\ndecreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%),\ndecreased lymphocyte count (58%), decreased platelet count (51%), increased\naspartate aminotransferase (45%), increased alanine aminotransferase (44%),\nincreased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite\n(34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%),\nconstipation (28%), decreased sodium (22%), stomatitis (20%), and upper\nrespiratory tract infection (20%).\n\nUse in Specific Populations\n\n\n * Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman.\nAdvise patients of the potential risks to a fetus. There are clinical\nconsiderations if ENHERTU is used in pregnant women, or if a patient becomes\npregnant within 7 months after the last dose of ENHERTU.\n\n * Lactation: There are no data regarding the presence of ENHERTU in human milk,\nthe effects on the breastfed child, or the effects on milk production. Because\nof the potential for serious adverse reactions in a breastfed child, advise\nwomen not to breastfeed during treatment with ENHERTU and for 7 months after\nthe last dose.\n\n * Females and Males of Reproductive Potential: Pregnancy testing: Verify\npregnancy status of females of reproductive potential prior to initiation of\nENHERTU. Contraception: Females: ENHERTU can cause fetal harm when\nadministered to a pregnant woman. Advise females of reproductive potential to\nuse effective contraception during treatment with ENHERTU and for 7 months\nafter the last dose. Males: Advise male patients with female partners of\nreproductive potential to use effective contraception during treatment with\nENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair\nmale reproductive function and fertility.\n\n * Pediatric Use: Safety and effectiveness of ENHERTU have not been established\nin pediatric patients.\n\n * Geriatric Use: ENHERTU as Monotherapy: Of the 2233 patients treated with\nENHERTU 5.4 mg/kg, 28% were ≥65 years and 6% were ≥75 years. No overall\ndifferences in efficacy within clinical studies were observed between patients\n≥65 years compared to younger patients. There was a higher incidence of\nGrade 3-4 adverse reactions observed in patients aged ≥65 years (56%) as\ncompared to younger patients (49%). Of the 125 patients with HER2-positive\nlocally advanced or metastatic gastric or GEJ adenocarcinoma treated with\nENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were\n≥75 years. No overall differences in efficacy or safety were observed\nbetween patients ≥65 years of age compared to younger patients. ENHERTU in\nCombination with Pertuzumab: In patients with HER2-positive unresectable or\nmetastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with\npertuzumab (N=431), 17% were ≥65 years and 3% were ≥75 years. No overall\ndifferences in efficacy or safety were observed between patients ≥65 years\ncompared to younger patients. ENHERTU followed by THP: Of the 320 patients\nwith HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed\nby THP, 12% were ≥65 years and 1.6% were ≥75 years. No overall differences\nin efficacy were observed between patients ≥65 years compared to younger\npatients. There was a higher incidence of Grade 3-4 adverse reactions observed\nin patients ≥65 years (38%) as compared to younger patients (30%).\n\n * Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been\nobserved in patients with moderate renal impairment. Monitor patients with\nmoderate renal impairment more frequently. The recommended dosage of ENHERTU\nhas not been established for patients with severe renal impairment (CLcr\n<30 mL/min).\n\n * Hepatic Impairment: In patients with moderate hepatic impairment, due to\npotentially increased exposure, monitor for increased adverse reactions\nrelated to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU\nhas not been established for patients with severe hepatic impairment (total\nbilirubin >3 times ULN and any AST).\n\nTo report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at\n1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.\n\nPlease see accompanying full Prescribing Information\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Prescribing+Information&index=31&md5=588fdaf74ae51b1738e50aad0f7ea490)\n, including Boxed WARNINGS, and Medication Guide\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdsi.com%2Fprescribing-information-portlet%2FgetPIContent%3FproductName%3DEnhertu_Med%26inline%3Dtrue&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Medication+Guide&index=32&md5=2f06e990c95a94bcda7dbeb7ee6254d7)\n.\n\nAbout the ADC Portfolio of Daiichi Sankyo\n\nThe Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical\ndevelopment crafted from ADC technology discovered in-house by Daiichi Sankyo.\n\nThe DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in\nclinical development where each ADC is comprised of a monoclonal antibody\nattached to a number of topoisomerase I inhibitor payloads (an exatecan\nderivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs\ninclude Enhertu and Datroway, which are being jointly developed and\ncommercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd),\nraludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are\nbeing jointly developed and commercialized globally with Merck & Co., Inc,\nRahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo.\n\nAn additional ADC being developed by Daiichi Sankyo is DS3610, which consists\nof an antibody attached to a novel payload that acts as an agonist of STING.\n\nIfinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939,\nDS3610 and DS3790 are investigational medicines that have not been approved\nfor any indication in any country. Safety and efficacy have not been\nestablished.\n\nAbout Daiichi Sankyo\n\nDaiichi Sankyo (TSE: 4568) is a global healthcare company committed to\nbecoming a trusted healthcare innovator, transforming the lives of people\nthrough its strength in science and technology. The company discovers and\ndevelops new standards of care to address diverse medical needs to fulfill its\npurpose of contributing to the enrichment of quality of life around the world.\nWith a strategic focus on oncology, Daiichi Sankyo is advancing an\nindustry-leading antibody drug conjugate portfolio along with identifying new\nbreakthrough generating technologies to deliver practice-changing medicines to\npatients, healthcare professionals and society. For more information, please\nvisit www.daiichisankyo.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.daiichisankyo.com&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=www.daiichisankyo.com&index=33&md5=54666999315767a4dae9a3b90dbea9f8)\n.\n\nDisclosure: Dr. Modi provides consulting and advisory services to Daiichi\nSankyo (and AstraZeneca).\n\nReferences:\n\n(1) World Health Organization. Breast Fact Sheet\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fgco.iarc.who.int%2Fmedia%2Fglobocan%2Ffactsheets%2Fcancers%2F20-breast-fact-sheet.pdf&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Breast+Fact+Sheet&index=34&md5=bf4746e49b88d05946cb44149354e636)\n. Accessed May 2026.\n\n(2) Siegel RL, et al. CA Cancer J Clin\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Facsjournals.onlinelibrary.wiley.com%2Fdoi%2F10.3322%2Fcaac.70043&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=CA+Cancer+J+Clin&index=35&md5=ad6addf8deacf17bee3f3a5342d010a8)\n. 2026;76(1):e70043.\n\n(3) Cheng X. Genes\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.mdpi.com%2F2073-4425%2F15%2F7%2F903&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Genes&index=36&md5=8096b2528f23799c376479b8e2316dba)\n(Basel). 2024;15(7):903.\n\n(4) Tarantino P, et al. Ann Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252823%252900693-2%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Ann+Oncol&index=37&md5=7769963882eba6f971a338c95c8be419)\n. 2023;34(8):645-659.\n\n(5) Mahtani R, et al. Cancers\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.mdpi.com%2F2072-6694%2F17%2F11%2F1848&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Cancers&index=38&md5=50356515713ae436eec5e84f252f6581)\n(Basel). 2025;17(11):1848.\n\n(6) Wang J, et al. Breast Cancer\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fdoi.org%2F10.2147%2FBCTT.S432526&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Breast+Cancer&index=39&md5=e9f962557f2118d8170ebd594bbfcc8c)\n. 2023;15:721-730.\n\n(7) Spring LM, et al. Clin Cancer Res\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Faacrjournals.org%2Fclincancerres%2Farticle-abstract%2F26%2F12%2F2838%2F82378%2FPathologic-Complete-Response-after-Neoadjuvant%3FredirectedFrom%3Dfulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Clin+Cancer+Res&index=40&md5=e3d0a6fef017e3a60e142c543cdf837c)\n. 2020;26(12):2838-2848.\n\n(8) Schneeweiss A, et al. Ann Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252819%252936929-7%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Ann+Oncol&index=41&md5=788b05ddcdfcec47b1156b0579859393)\n. 2013;24(9):2278-2284.\n\n(9) Swain SM, et al. Ann Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.annalsofoncology.org%2Farticle%2FS0923-7534%252819%252935495-X%2Ffulltext&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Ann+Oncol&index=42&md5=c3bbb27dc3da1b6b264f5cdd91117aa0)\n. 2018;29(3):646-653.\n\n(10) Huober J, et al. J Clin Oncol\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fascopubs.org%2Fdoi%2F10.1200%2FJCO.21.02772%3Furl_ver%3DZ39.88-2003%26rfr_id%3Dori%3Arid%3Acrossref.org%26rfr_dat%3Dcr_pub%2520%25200pubmed&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=J+Clin+Oncol&index=43&md5=b6c432008c65d749e586d9fa4b89310f)\n. 2022;40(25):2946-2956.\n\n(11) Masuda N, et al. Breast Cancer Res Treat\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs10549-020-05524-6&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=Breast+Cancer+Res+Treat&index=44&md5=f6d9ebca3d55350cc703aac67cfb9cf9)\n. 2020;180(1):135-146.\n\n(12) Gao HF, et al. Presented at ASCO Annual Meeting 2025.\n\n(13) Geyer CE, et al. N Engl J Med\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nejm.org%2Fdoi%2F10.1056%2FNEJMoa2406070%3Furl_ver%3DZ39.88-2003%26rfr_id%3Dori%3Arid%3Acrossref.org%26rfr_dat%3Dcr_pub%2520%25200pubmed&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=N+Engl+J+Med&index=45&md5=2f836eaa7f5e8445c87746ba75749b37)\n. 2025;392:249-257.\n\n(14) National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer.\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fseer.cancer.gov%2Fstatfacts%2Fhtml%2Fbreast.html&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=SEER+Cancer+Stat+Facts%3A+Female+Breast+Cancer.&index=46&md5=c08af5fac7a2f41f96d92c62cf42a261)\nAccessed May 2026.\n\n(15) von Minckwitz G, et al. N Engl J Med\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F30516102%2F&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=N+Engl+J+Med&index=47&md5=f7e78a6b3c8a5acf1cfcfcc09afd9afe)\n. 2019;380(7):617-628.\n\n(16) Zaborowski AM and Wong SM. BJS.\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Facademic.oup.com%2Fbjs%2Farticle%2F110%2F7%2F765%2F7145840&esheet=54535775&newsitemid=20260513022601&lan=en-US&anchor=BJS.&index=48&md5=3e9dabbeea043f0382ad9164dca260fe)\n2023;110(7):765-772.\n\nPP-US-ENB-5118-1\n\n05/26\n\n\n\nView source version on businesswire.com:\nhttps://www.businesswire.com/news/home/20260513022601/en/\n(https://www.businesswire.com/news/home/20260513022601/en/)\n\nMEDIA CONTACTS: \n\nGlobal: \n\nJennifer Brennan\n\njennifer.brennan@daiichisankyo.com \n(mailto:jennifer.brennan@daiichisankyo.com) \n+1 908 900 3183 (mobile)\n\n\n\nJapan: \n\nDS-PR_jp@daiichisankyo.com \n(mailto:DS-PR_jp@daiichisankyo.com) \n\n\nINVESTOR RELATIONS CONTACT: \n\nDaiichiSankyoIR_jp@daiichisankyo.com\n(mailto:DaiichiSankyoIR_jp@daiichisankyo.com)\n\n\nCopyright Business Wire 2026"},"type":"article","timestamp":"2026-05-15T22:31:00.155666066Z","server_sent_at_ms":1778884260155},"received_at":"2026-05-15T22:31:00.507Z","source_url":"https://www.businesswire.com/news/home/20260513022601/en/"},"analysis":{"id":"26495","press_release_id":"37051","analysis_json":{"industry":{"label":"Pharmaceuticals, Biotechnology & Life Sciences","sector":"Health Care"},"redFlags":[],"eventType":"fda_approval","narrative":"The FDA has approved Enhertu for two new indications in HER2-positive early breast cancer: neoadjuvant treatment before surgery and adjuvant treatment after surgery for patients with residual disease.\n\nThe neoadjuvant approval is based on the DESTINY-Breast11 Phase 3 trial, which showed a 67.3% pathologic complete response rate versus 56.3% for the control regimen. The adjuvant approval relies on DESTINY-Breast05, which demonstrated a 53% reduction in the risk of invasive disease recurrence or death compared to T-DM1.\n\nThese approvals expand Enhertu’s U.S. label to nine total indications, covering both early and metastatic settings. 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The adjuvant approval relies on DESTINY-Breast05, which demonstrated a 53% reduction in the risk of invasive disease recurrence or death compared to T-DM1.\n\nThese approvals expand Enhertu’s U.S. label to nine total indications, covering both early and metastatic settings. 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