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Apr 13, 2026

Based on results from IDeate-Lung01 phase 2 trial, with support from IDeate-PanTumor01 phase 1/2 trial If approved, ifinatamab deruxtecan would be a first-in-class B7-H3 directed DXd antibody drug conjugate for these patients   Basking Ridge, NJ – (April 13, 2026) – Daiichi Sankyo (TSE: 4568) and Merck’s, known as MSD outside of the United States and Canada, (NYSE: MRK) Biologics License Application (BLA) for ifinatamab deruxtecan (I-DXd) has been accepted and granted Priority Review by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.  Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck. The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The FDA is also reviewing the BLA under the Real-Time Oncology Review (RTOR) program and Project Orbis, two initiatives of the FDA which are designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for its regulatory decision, is October 10, 2026.   The BLA is based on results from the IDeate-Lung01 phase 2 trial, with support from the IDeate-PanTumor01 phase 1/2 trial. Results from the primary analysis of IDeate-Lung01 were presented at the 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC25) and published in the Journal of Clinical Oncology. Ifinatamab deruxtecan also was previously granted Breakthrough Therapy Designation by the FDA in August 2025 for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.  “The FDA’s granting of Priority Review for ifinatamab deruxtecan marks a significant milestone in our effort to provide new and innovative treatment options for patients with extensive-stage small cell lung cancer,” said John Tsai, MD, Global Head, R&D, Daiichi Sankyo. “We look forward to continuing to work with the FDA to bring this potential first-in-class B7-H3 directed DXd antibody drug conjugate to patients as quickly as possible.”  “Small cell lung cancer remains one of the toughest cancers to treat, with few options if the disease progresses after standard of care treatments,” said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. “The FDA’s acceptance of the BLA reinforces the important role that ifinatamab deruxtecan could play in helping to address the needs of patients with extensive-stage small cell lung cancer.”  About IDeate-Lung01 IDeate-Lung01 is a global, multicenter, randomized, open-label, two-part phase 2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with ES-SCLC who were previously treated with at least one prior line of platinum-based chemotherapy and a maximum of three prior lines of therapy. Patients with asymptomatic brain metastases (untreated or previously treated) were eligible to participate.  In the first part of the trial (dose optimization), patients were randomized 1:1 to receive ifinatamab deruxtecan (8 or 12 mg/kg) given intravenously once every three weeks. In the second part of the trial (dose expansion), patients received ifinatamab deruxtecan (12 mg/kg) intravenously at the same dosing interval.  The primary endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), time to response (TTR), overall survival (OS), pharmacokinetics and safety. Intracranial ORR was assessed by BICR as an exploratory analysis.  IDeate-Lung01 enrolled 187 patients in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.  About IDeate-PanTumor01 IDeate-PanTumor01 is a global, multicenter, first-in-human, open-label phase 1/2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists. The phase 1 part of the trial (dose escalation) is assessing the safety and tolerability of increasing doses of ifinatamab deruxtecan to determine the maximum tolerated dose and recommended dose for expansion (RDE). The phase 2 part of the trial (dose expansion) is evaluating the safety and efficacy of ifinatamab deruxtecan at the RDE of 12 mg/kg in patients with squamous non-small cell lung cancer, metastatic castration-resistant prostate cancer or esophageal squamous cell carcinoma. The dose escalation part of the trial is evaluating dose-limiting toxicity and safety. The dose expansion part of the trial is evaluating ORR, DOR, DCR, PFS, OS and safety. Pharmacokinetic endpoints, exploratory biomarker and immunogenicity endpoints also will be assessed.   IDeate-PanTumor01 will enroll approximately 250 patients in Asia and North America. For more information about the trial, visit ClinicalTrials.gov.  About Small Cell Lung Cancer Approximately 250,000 patients are diagnosed with small cell lung cancer (SCLC) each year globally.1 There were approximately 27,000 new cases of SCLC in the U.S. in 2025, accounting for about 12% of all lung cancer cases.2,3  SCLC is aggressive and progresses rapidly to the distant metastatic stage, which has a low five-year survival rate.4,5  While conventional standard of care treatments for patients with advanced SCLC may help improve outcomes, there is a need for additional subsequent treatment approaches.6,7,8,9  About B7-H3  B7-H3 is a transmembrane protein that belongs to the B7 family of proteins, which bind to the CD28 family of receptors that includes PD-1.10,11  B7-H3 is overexpressed in a wide range of cancer types, including SCLC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target.12,13,14,15  There are currently no B7-H3 directed medicines approved for the treatment of cancer. About Ifinatamab Deruxtecan  Ifinatamab deruxtecan is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.  Ifinatamab deruxtecan was granted Breakthrough Therapy Designation by the FDA for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.     Ifinatamab deruxtecan has been granted Orphan Drug Designation (ODD) by the U.S. FDA, European Commission, Japan Ministry of Health, Labour and Welfare and Taiwan Food and Drug Administration for the treatment of SCLC. Ifinatamab deruxtecan also was granted ODD for the treatment of esophageal cancer by the FDA. About the Ifinatamab Deruxtecan Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ifinatamab deruxtecan monotherapy and in combination with other cancer medicines across multiple cancers. The program is currently comprised of three phase 3 trials in advanced/metastatic disease, including SCLC (IDeate-Lung02), castration-resistant prostate cancer (IDeate-Prostate01) and esophageal squamous cell carcinoma (IDeate-Esophageal01).  About the Daiichi Sankyo and Merck  Daiichi Sankyo and Merck, known as MSD outside of the United States and Canada, entered into a global collaboration in October 2023 to jointly develop and commercialize ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In August 2024, the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck & Co., Inc., Rahway, N.J., USA will maintain exclusive rights. Merck & Co., Inc., Rahway, N.J., USA will be solely responsible for manufacturing and supply for gocatamig. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo.    The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include ENHERTU® and DATROWAY®, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc., Rahway, N.J., USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo.    An additional ADC being developed by Daiichi Sankyo is DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING.  Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610 and DS3790 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo  Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com.  Merck’s Focus on Cancer  Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 20 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology.  About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).   Media Contacts: Daiichi Sankyo Global/US: Jennifer Brennan Daiichi Sankyo jennifer.brennan@daiichisankyo.com +1 908 900 3183 (mobile)   Japan: Daiichi Sankyo Co., Ltd. DS-PR_jp@daiichisankyo.com Investor Relations Contact: DaiichiSankyoIR_jp@daiichisankyo.com   Merck Media: Julie Cunningham julie.cunningham@merck.com   Michael McArdle michael.mcardle@merck.com   Investors Peter Dannenbaum  (732) 594-1579  Steven Graziano (732) 594-1583   References: 1 Wang Q, et al. Journal of Thoracic Oncology. 2023 Jan;18(1):31-46. 2 National Cancer Institute. SEER Explorer. Cancer Stat Facts: Lung and Bronchus Cancer. Accessed December 2025. 3 U.S. Centers for Disease Control and Prevention. United States Cancer Statistics. Types of Lung Cancer | U.S. Cancer Statistics | CDC. Accessed December 2025. 4 Rudin CM, et al. Nat Rev Dis Primers. 2021;7(1):3.  5 National Cancer Institute. SEER Explorer. Small cell carcinoma of the Lung and Bronchus: 5-year Relative Survival. Accessed January 2026. 6 American Cancer Society. Treatment Choices for Small Cell Lung Cancer, by Stage. Accessed January 2026.  7 Liu SV, et al. J Clin Oncol. 2021;39(6):619-30.  8 Paz-Ares L, et al. ESMO Open. 2022;7(2):100408.  9 von Pawel J, et al. J Clin Oncol. 2014; 32:4012-4019. 10 Zhao B, et al. J Hematol Oncol. 2022;15(1):153.  11 Janakiram M, et al. Immunol Rev. 2017;276(1):26-39. 12 Qiu M-j, et al. Front. Oncol. 2021;11:600238.  13 Picarda E, et al. Clin Cancer Res. 2016;22(14):3425-3431. 14 Bendell JC, et al. J Clin Oncol. 2020;39(15 suppl 1). Abstract TPS3646. 15 Kontos F, et al. Clin Cancer Res. 2021;27(5):1227-1235.

Mar 9, 2026

Tokyo and Basking Ridge, NJ – (March 9, 2026) – Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/NYSE: AZN) supplemental Biologics License Application (sBLA) for ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been accepted and granted Priority Review in the U.S. for the treatment of adult patients with HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have residual invasive disease after neoadjuvant HER2 targeted treatment. ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. The U.S. Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant benefit over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA in December 2025 for ENHERTU based on data from the DESTINY-Breast05 phase 3 trial presented at the 2025 European Society of Medical Oncology (#ESMO25) Congress and subsequently published in The New England Journal of Medicine. The Prescription Drug User Fee Act (PDUFA) date, the FDA target action date for their regulatory decision, is July 7, 2026. Results from DESTINY-Breast05 showed ENHERTU significantly reduced the risk of invasive disease recurrence or death (invasive disease-free survival [IDFS]) by 53% (hazard ratio [HR]=0.47; 95% confidence interval [CI]: 0.34-0.66; p<0.0001) compared to trastuzumab emtansine (T-DM1) as a post-neoadjuvant treatment for patients with HER2 positive breast cancer with residual invasive disease following neoadjuvant therapy. Trial results demonstrated a three-year IDFS rate of 92.4% (95% CI: 89.7-94.4) in the ENHERTU arm compared to 83.7% with T-DM1 (95% CI: 80.2-86.7). IDFS findings were consistent across all prespecified subgroups. Data also showed that ENHERTU significantly reduced the risk of disease recurrence or death by 53% (HR=0.47; 95% CI: 0.34-0.66; p<0.0001) compared to T-DM1. Treatment with ENHERTU in DESTINY-Breast05 also reduced the risk of distant disease recurrence (distant recurrence-free interval [DRFI]) by 51% (HR=0.49; 95% CI: 0.34-0.71) and the risk of brain metastases (brain metastasis-free interval [BMFI]) by 36% (HR=0.64; 95% CI: 0.35-1.17) versus T-DM1.  The sBLA is being reviewed under Project Orbis, which provides a framework for the concurrent submission and review of oncology medicines among participating international partners. This initiative is designed to bring effective cancer treatments to patients as early as possible. “For patients with residual invasive disease after neoadjuvant therapy, identifying additional treatments following surgery is critical to help further reduce the risk of recurrence and help prevent progression to metastatic disease,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “This Priority Review reinforces the potential of ENHERTU to become a new standard of care for HER2 positive early breast cancer based on the results of DESTINY-Breast05.” “While there has been significant progress in treating HER2 positive early breast cancer, managing patients at a higher risk of recurrence remains challenging,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “With this Priority Review, we move closer to bringing ENHERTU to the post-neoadjuvant setting, offering more patients the opportunity for sustained long-term outcomes and a potential path to cure.” The safety profile of ENHERTU observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified. Grade 3 or higher treatment emergent adverse event (TEAE) rates were comparable between ENHERTU (50.6%) and T-DM1 (51.9%). The most common grade 3 or higher TEAEs occurring in 5% or more of patients treated with ENHERTU were decreased neutrophil count (15.5%), decreased white blood cell count (10.1%), decreased platelet count (6.7%) and neutropenia (8.1%). Rates of interstitial lung disease (ILD) or pneumonitis were low in both arms with ILD events occurring in 9.6% of the ENHERTU arm and 1.6% of the T-DM1 arm. The majority of ILD or pneumonitis events were low grade (grade 1 [ENHERTU=16; 2.0%; T-DM1=8; 1.0%] or grade 2 [ENHERTU=52; 6.5%; T-DM1=5; 0.6%]). There were no grade 3 or higher ILD or pneumonitis events for T-DM1. In the ENHERTU arm, there were seven grade 3 events (0.9%) and two grade 5 events (0.2%) as determined by an independent adjudication committee. Regulatory submissions for ENHERTU based on DESTINY-Breast05 are under review in the EU and Japan. In addition, an sBLA for ENHERTU followed by paclitaxel, trastuzumab and pertuzumab (THP) currently is under review in the U.S. for the neoadjuvant treatment of adult patients with HER2 positive (IHC 3+ or ISH+) stage 2 or stage 3 breast cancer based on results from the DESTINY-Breast11 trial with a PDUFA date of May 18, 2026.    About DESTINY-Breast05 DESTINY-Breast05 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive early breast cancer with residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.  The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS, which is defined as the time from randomization until first invasive local, axillary or distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed DFS. Other secondary endpoints include overall survival, DRFI, BMFI, interval and safety.  DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov. About Post-Neoadjuvant Treatment for HER2 Positive Early Breast Cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.  More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1  In the U.S., more than 320,000 cases of breast cancer are diagnosed annually with more than 42,000 deaths. 2  HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer.3   HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.3  Approximately one in five cases of breast cancer is considered HER2 positive. 4  For patients with HER2 positive early breast cancer, achieving pathologic complete response (pCR) with neoadjuvant treatment is the earliest indicator of improved long-term survival.5   However, approximately half of patients who receive neoadjuvant treatment do not experience pCR, putting them at increased risk of disease recurrence.6,7,8,9,10  Despite receiving additional treatment for residual disease in the post-neoadjuvant setting, some patients still experience invasive disease or death and current treatment options have shown limited impact on central nervous system recurrence.11   Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to approximately 30%. 12 Post-neoadjuvant therapy represents a key opportunity to minimize the risk of recurrence and prevent progression to metastatic disease for patients with residual disease. New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients. 13,14 About ENHERTU  ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.  ENHERTU (5.4 mg/kg) in combination with pertuzumab is approved in the U.S. as a first-line treatment for adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test, based on the results from the DESTINY-Breast09 trial. ENHERTU (5.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.  ENHERTU (5.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. ENHERTU (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. ENHERTU (5.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4 mg/kg) is approved in more than 80 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric04 trials.  ENHERTU (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.  About the ENHERTU Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable cancers.  About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY® in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and DATROWAY. About the ADC Portfolio of Daiichi Sankyo  The Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo. The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include ENHERTU and DATROWAY, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo. An additional ADC being developed by Daiichi Sankyo is DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING.  Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610 and DS3790 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. ENHERTU U.S. Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated: HER2-Positive Metastatic Breast Cancer In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy   HER2-Low and HER2-Ultralow Metastatic Breast Cancer As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting   As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy   HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC) As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.   HER2-Positive Locally Advanced or Metastatic Gastric Cancer As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen   HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Important Safety Information WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception. Contraindications None. Warnings and Precautions Interstitial Lung Disease / Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU monotherapy or ENHERTU in combination with pertuzumab. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21). Neutropenia Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU monotherapy or ENHERTU in combination with pertuzumab. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level. HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1.2% of patients. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients. Left Ventricular Dysfunction Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment. HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were Grade 3 or 4. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Embryo-Fetal Toxicity ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU. Additional Dose Modifications Thrombocytopenia For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level. Adverse Reactions HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 38% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%). ENHERTU in Combination with Pertuzumab The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients, 86% were exposed for >6 months and 73% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea (74%), increased alanine aminotransferase (65%), diarrhea (64%), increased aspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased platelet count (55%), increased blood alkaline phosphatase (54%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (32%), constipation (31%), decreased appetite (31%), decreased weight (28%), musculoskeletal pain (23%), abdominal pain (22%), and increased blood bilirubin (23%). HER2-Positive Metastatic Breast Cancer DESTINY-Breast09 The safety of ENHERTU 5.4 mg/kg in combination with pertuzumab was evaluated in DESTINY-Breast09, a randomized, three-arm, multicenter study including 763 patients with HER2-positive (IHC 3+ or ISH+) unresectable or metastatic breast cancer. Three hundred eighty-one patients received ENHERTU in combination with pertuzumab and 382 patients received THP (taxane [docetaxel or paclitaxel], trastuzumab, and pertuzumab). Among patients who received ENHERTU in combination with pertuzumab, the median duration of treatment was 22 months (range: 0.3 months to 44.5 months). Serious adverse reactions occurred in 27% of patients receiving ENHERTU in combination with pertuzumab. Serious adverse reactions in >1% of patients were diarrhea, pneumonia, febrile neutropenia, hypokalemia, vomiting, ILD, pulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred in 3.4% of patients including pneumonia (n=3), ILD (n=2), sepsis (n=2), pulmonary embolism, septic shock, acute kidney injury, dyspnea, febrile neutropenia, and intestinal ischemia (one patient each). ENHERTU was discontinued for adverse reactions in 21% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis (6.6%). Dose interruptions due to adverse reactions occurred in 69% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, neutropenia, upper respiratory tract infection, fatigue, anemia, hypokalemia, ILD/pneumonitis, thrombocytopenia, pneumonia, diarrhea, transaminase increased, leukopenia, cough, pyrexia, decreased appetite, and blood bilirubin increased. Dose reductions occurred in 46% of patients treated with ENHERTU in combination with pertuzumab. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, neutropenia, nausea, diarrhea, ILD/pneumonitis, thrombocytopenia, vomiting, transaminases increased, decreased weight, febrile neutropenia, and hypokalemia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (87%), decreased hemoglobin (80%), decreased neutrophil count (78%), nausea (75%), increased alanine aminotransferase (66%), diarrhea (64%), increased aspartate aminotransferase (62%), decreased lymphocyte count (62%), decreased platelet count (56%), increased blood alkaline phosphatase (55%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (33%), constipation (33%), decreased appetite (32%), decreased weight (30%), COVID-19 (28%), musculoskeletal pain (24%), increased blood bilirubin (23%), and abdominal pain (23%). DESTINY-Breast03 The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU. Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each). ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%). HER2-Low and HER2-Ultralow Metastatic Breast Cancer DESTINY-Breast06 The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU. Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each). ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%). DESTINY-Breast04 The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU. Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each). ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%). HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg) DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis. The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY‑Lung02. Nineteen percent of patients were exposed for >6 months. Serious adverse reactions occurred in 30% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%). ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, decreased blood potassium, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%). HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU. Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient each (0.8%). ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%). HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2). Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock. ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%). Use in Specific Populations Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU. Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose. Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility. Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients. Geriatric Use: ENHERTU as Monotherapy: Of the 2355 patients with HER2-positive, HER2-low, or HER2-ultralow breast cancer treated with ENHERTU 5.4 mg/kg, 23% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (55%) as compared to younger patients (50%). Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02, 39% were ≥65 years and 9% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. ENHERTU in Combination with Pertuzumab: In patients with HER2-positive unresectable or metastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), 17% were ≥65 years and 3% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min). Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST). To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA  at 1-800-FDA-1088 or fda.gov/medwatch. Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com. Media Contacts: Global/US: Jennifer Brennan Daiichi Sankyo jennifer.brennan@daiichisankyo.com +1 908 900 3183 (mobile)   Japan: Daiichi Sankyo Co., Ltd. DS-PR_jp@daiichisankyo.com Investor Relations Contact: DaiichiSankyoIR_jp@daiichisankyo.com References 1 World Health Organization. Breast Fact Sheet. Accessed March 2026. 2 Siegel RL, et al. CA Cancer J Clin. 2026;76(1):e70043. 3 Cheng X. Genes. 2024;15(7):903. 4 Tarantino P, et al. Ann Oncol. 2023;34(8):645-659. 5 Spring LM, et al. Clin Cancer Res. 2020;26(12):2838-2848. 6 Schneeweiss A, et al. Ann Oncol. 2013;24(9):2278-2284. 7 Swain SM, et al. Ann Oncol. 2018;29(3):646-653. 8 Huober J, et al. J Clin Oncol. 2022;40(25):2946-2956. 9 Masuda N, et al. Breast Cancer Res Treat. 2020;180(1):135-146. 10 Gao HF, et al. Presented at ASCO Annual Meeting 2025. 11 Geyer CE, et al. N Engl J Med. 2025;392(3):249-257. 12 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer. Accessed March 2026. 13 von Minckwitz G, et al. N Engl J Med. 2019;380(7):617-628. 14 Zaborowski AM and Wong SM. Br J Surg. 2023;110(7):765-772.