Datopotamab Deruxtecan

TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--The first patient has been dosed in the randomization phase of the DESTINY-Ovarian01 phase 3 trial evaluating ENHERTU® (trastuzumab deruxtecan) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab. DESTINY-Ovarian01 is being conducted in collaboration with the European Network of Gynecological Oncological Trial Groups (ENGOT), with the Spanish cooperative group (GEICO) as the lead ENGOT group, The GOG Foundation, Inc. (GOG-F) and Asia-Pacific Gynecologic Oncology Trials Group (APGOT). ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). The prognosis for patients with ovarian cancer is poor with an estimated five-year survival rate of 31.8% for those with advanced disease.1 Approximately 70% to 80% of patients with advanced ovarian cancer (Stage 3 or 4) will experience disease recurrence following standard treatment with surgery and platinum-based chemotherapy regimens.2 Maintenance therapy may be given to delay relapse and current recommended treatment strategies include bevacizumab or PARP inhibitor monotherapy or bevacizumab/PARP inhibitor combination treatment, depending on the biomarker status of the tumor.3 There currently are no HER2 directed medicines approved as maintenance therapy despite HER2 expression being present in up to 55% of ovarian cancers.4,5,6 “Results from the ovarian cancer cohort of DESTINY-PanTumor02 demonstrated clinically meaningful and durable responses in previously treated patients with HER2 expressing advanced ovarian cancer, supporting the development of ENHERTU in earlier lines of therapy,” said Abderrahmane Laadem, MD, Head, Late-Stage Oncology Clinical Development, Daiichi Sankyo. “Given the important role first-line maintenance therapy can play in disease control, we have initiated this first phase 3 trial in ovarian cancer to evaluate whether ENHERTU combined with bevacizumab could become a new maintenance strategy for patients with HER2 expressing advanced high-grade epithelial ovarian cancer.” About DESTINY-Ovarian01 DESTINY-Ovarian01 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab. The randomized period of the trial was preceded by a non-randomized safety run-in phase to evaluate the safety of ENHERTU in combination with bevacizumab. The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the HER2 IHC 3+/2+ population. The key secondary endpoint is overall survival (OS) in the HER2 IHC 3+/2+ population. Additional secondary endpoints include PFS as assessed by BICR and OS in the HER2 IHC 3+/2+/1+ population as well as PFS as assessed by investigator in both the HER2 IHC 3+/2+ and HER2 IHC 3+/2+/1+ populations. DESTINY-Ovarian01 will enroll approximately 580 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov. About Ovarian Cancer Ovarian cancer is the third most common gynecologic cancer and the seventh most common cancer among women worldwide.7 More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.8 The prognosis for ovarian cancer is poor with an estimated five-year survival rate of 31.8% for those with advanced disease.1 Epithelial ovarian cancer accounts for approximately 90% of ovarian cancer cases and the majority are diagnosed at an advanced stage (Stage 3 or 4).9 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors.10 HER2 expression (IHC 3+/2+/1+) is present in up to 55% of ovarian cancers and is associated with advanced stages, higher frequency of recurrence, shorter survival time and lower response to platinum-based chemotherapy.4,5,6,11 Approximately 70% to 80% of patients with advanced ovarian cancer (Stage 3 or 4) will experience disease recurrence following standard treatment with surgery and platinum-based chemotherapy regimens.2 Maintenance therapy may be given to delay relapse and current recommended treatment strategies include bevacizumab or PARP inhibitor monotherapy or bevacizumab/PARP inhibitor combination treatment, depending on the biomarker status of the tumor.3 As a majority of patients will experience disease progression on or after these therapies, new treatment strategies are needed.12,13,14,15 Currently, there are no HER2 targeted medicines approved as first-line maintenance therapy for patients with HER2 expressing advanced epithelial ovarian cancer.16,17 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) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization [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 85 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 45 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 60 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 70 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-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 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 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 six 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 is being developed by Daiichi Sankyo. Additional ADCs being developed by Daiichi Sankyo include DS-9606, which consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload and DS3610, which consists of an antibody attached to a novel immunomodulatory payload that acts as an agonist of STING. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS-9606 and DS3610 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. ENHERTU U.S. Indications and Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) 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 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 – 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 Unresectable or metastatic non-small cell lung cancer (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. 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 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. WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY 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. 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) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors 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. 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. 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) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors 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. 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 20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF 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) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors 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. 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) 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%). HER2-Positive Metastatic Breast Cancer 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: Of the 1741 patients with HER2-positive, HER2-low, or HER2-ultralow breast cancer treated with ENHERTU 5.4 mg/kg, 24% were ≥65 years and 4.9% 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 (61%) as compared to younger patients (52%). 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. 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. _________________________________ References: 1 National Cancer Institute. Cancer Stat Facts: Ovarian Cancer. Updated 2021. Accessed December 2025. 2 Pignata S, et al. Ann Oncol. 2017 Nov 1;28(suppl_8):viii51-viii56. 3 Ray-Coquard I, et al. N Engl J Med. 2019;381:2416-28. 4 Uzunparmak B, et al. Ann Oncol. 2023;34 (11):1035-46. 5 Chung Y, et al. J Gyn Oncol. 2019;379(26):2495-2505. 6 Kim Y-N, Nature. et al. 2024;28(suppl_8):viii51-viii56. 7 Globocan 2022. International agency for research on cancer (IARC): Age-Standardized Rate (World) per 100 000, Incidence and Mortality, Females, all ages in 2022. Accessed December 2025. 8 Global Cancer Observatory. Population Fact Sheet. Updated 2022. Accessed December 2025. 9 Torre LA, et al. CA Cancer J Clin. 2018;68(4):284-296. 10 Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-25. 11 Serrano-Olvera A, et al. Cancer Treat Rev. 2006;32(3):180-190. 12 Ray-Coquard I, et al. Ann Oncol. 2023 Aug;34(8):681-692. 13 DiSilvestro P, et al. J Clin Oncol. 2023 Jan 20;41(3):609-617. 14 Monk BJ, et al. Ann Oncol. 2024 Nov;35(11):981-992. 15 Oza AM, et al. Lancet Oncol. 2015 Aug;16(8):928-36. 16 Monk BJ, et al. J Clin Oncol. 2022;40(34):3952-64. 17 Moore K, et al. N Engl J Med. 2018;379(26):2495-2505.

Additional data from DESTINY-Breast11, DESTINY-Breast05, DESTINY-Breast09, DESTINY-Breast03 and TROPION-Breast02 reinforce practice-changing results of ENHERTU ® and DATROWAY ® across a broad spectrum of patients with breast cancer Trials-in-progress across breast cancer portfolio of Daiichi Sankyo demonstrate company’s commitment to creating new standards of care Science & Technology Day to be held following SABCS to discuss R&D and oncology business updates TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) will present new breast cancer clinical research across its DXd antibody drug conjugate (ADC) portfolio from more than 30 abstracts at the 2025 San Antonio Breast Cancer Symposium (#SABCS25), which include four rapid fire mini-oral sessions and other presentations from five landmark trials of ENHERTU® (trastuzumab deruxtecan) and DATROWAY® (datopotamab deruxtecan) across a broad spectrum of breast cancer. Four rapid fire mini-oral sessions will feature ENHERTU data in the curative-intent and metastatic settings of HER2 positive breast cancer, including two presentations from the DESTINY-Breast11 phase 3 trial highlighting patient reported outcomes (RF6-06) and further safety analyses (RF6-02) of ENHERTU followed by paclitaxel, trastuzumab and pertuzumab (THP) compared to dose-dense doxorubicin and cyclophosphamide followed by THP (ddAC-THP) in the neoadjuvant setting (before surgery) in patients with high-risk, locally advanced HER2 positive early-stage breast cancer. Additional efficacy and safety data (RF6-01) from the DESTINY-Breast05 phase 3 trial comparing ENHERTU to trastuzumab emtansine (T-DM1) as a post-neoadjuvant (after surgery) therapy in patients with high-risk HER2 positive early breast cancer with residual invasive disease in the breast and/or axillary lymph nodes also will be highlighted. The fourth rapid fire presentation will feature patient reported outcomes (RF6-07) from the ENHERTU plus pertuzumab arm of the DESTINY-Breast09 phase 3 trial as a first-line treatment of HER2 positive metastatic breast cancer. Interim results from DESTINY-Breast09 were recently published in The New England Journal of Medicine, marking the eighth pivotal trial of ENHERTU to be published in the prestigious journal. Additional updates from two other landmark breast cancer trials include poster presentations featuring the final analysis and five-year follow-up of efficacy and safety data (PS5-01-30) from the DESTINY-Breast03 phase 3 trial comparing ENHERTU versus T-DM1 as a second-line treatment of HER2 positive metastatic breast cancer, and further safety analysis (PS5-03-05) from the TROPION-Breast02 phase 3 trial of DATROWAY, the first trial ever to demonstrate a significant improvement in overall survival compared to chemotherapy as first-line treatment for patients with locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) for whom immunotherapy is not an option. “Our latest research across these five landmark trials demonstrate how the DXd antibody drug conjugate portfolio of Daiichi Sankyo continues to potentially transform standards of care for patients with breast cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We remain committed to following the science and collaborating with the breast cancer community to create innovative medicines that advance the treatment of breast cancer.” Additional data from the DESTINY clinical trial program to be highlighted in poster presentations at SABCS include an exploratory post-hoc subgroup analysis by hormone receptor status from the DESTINY-Breast12 phase 3b/4 trial (PS5-01-27) of ENHERTU in patients with HER2 positive metastatic breast cancer and brain metastases; the final results from the ENHERTU monotherapy and ENHERTU plus pertuzumab arms of the DESTINY-Breast07 phase 1b/2 trial (PS5-01-14) in patients with previously untreated HER2 positive metastatic breast cancer; and, initial characteristics of first enrolled patients from the DESTINY Breast Respond HER2 Low Europe non-interventional study (PS5-08-14) of ENHERTU in HER2 low metastatic breast cancer. Collaborations Supporting Innovation in Breast Cancer Research Additional data presented at SABCS include results from four externally sponsored trials across the DXd ADC pipeline of Daiichi Sankyo. Two spotlight poster presentations will report interim results from the HALLOW prospective observational trial (PD13-11) evaluating the efficacy and safety of ENHERTU in patients with HER2 low (IHC 1+ or 2+/ISH-) metastatic breast cancer with and without active brain metastases in Japan, and a post-hoc pooled efficacy analysis (PD13-10) from the TUXEDO-3 phase 2 trial of patritumab deruxtecan (HER3-DXd) in patients with HER2 positive metastatic breast cancer and active brain metastases or leptomeningeal disease previously treated with ENHERTU. Results from cohorts 1 and cohorts 2 of the TUXEDO-3 trial were recently published in The Lancet Oncology and results from cohort 3 were published in Nature Medicine. Two poster presentations will report on the intracranial and/or extracranial activity of ENHERTU and DATROWAY. A translational ctDNA analysis of intracranial and extracranial activity (PS2-08-20) of ENHERTU from the DEBBRAH phase 2 trial in patients with HER2 positive and HER2 low breast cancer with leptomeningeal disease will be highlighted, as well as results of intracranial activity (PS1-09-02) of DATROWAY from the DATO-BASE phase 2 trial in patients with HER2 negative breast cancer with leptomeningeal disease. Trials-in-Progress Across Breast Cancer Portfolio of Daiichi Sankyo Several trials-in-progress poster presentations at SABCS further highlight research underway to address a broad spectrum of unmet needs for patients with breast cancer. Additional externally sponsored trials for ENHERTU and DATROWAY include the PONTIAC phase 2 trial (PS5-07-15) evaluating ENHERTU versus CDK4/6 inhibitor-based endocrine therapy as a first-line treatment of non-luminal HR positive, HER2 low and HER2 ultralow advanced breast cancer; a phase 1b trial (PS5-09-22) evaluating ENHERTU in combination with valemetostat, an EZH1/2 inhibitor, in patients with HER2 low, HER2 ultralow and HER2 null metastatic breast cancer; and the TROPION-Breast06 phase 3b trial (PS5-07-21) of DATROWAY in patients with HR positive, HER2 IHC 0 inoperable or metastatic breast cancer refractory to endocrine therapy. Three additional trials-in-progress from the HERTHENA clinical development program of patritumab deruxtecan (HER3-DXd) also will be highlighted. These include the HERTHENA-Breast04 phase 3 trial (PS5-07-22) evaluating patritumab deruxtecan versus physician’s choice of treatment in patients with HR positive, HER2 negative unresectable locally advanced or metastatic breast cancer; the HERTHENA-Breast03 phase 2 trial (PS5-12-21) evaluating neoadjuvant patritumab deruxtecan plus pembrolizumab before or after pembrolizumab plus chemotherapy in patients with high-risk early-stage TNBC or HR low positive/HER2 negative breast cancer; and, the HERTHENA-Breast01 phase 1b/2 trial (PS5-12-23) evaluating patritumab deruxtecan in combination with HER2 targeted agents in patients with HER2 positive unresectable locally advanced or metastatic breast cancer. Science & Technology Day Daiichi Sankyo will hold its annual Science & Technology Day for investors on Monday, December 15, 2025, from 5:30 to 7:30 pm ET / Tuesday, December 16, 2025, from 7:30 – 9:30 am JST. Executives from Daiichi Sankyo will provide an update on R&D, business and manufacturing developments across the portfolio. Daiichi Sankyo Presentation Highlights at SABCS Presentation Title Author Abstract Presentation (CST) ENHERTU (trastuzumab deruxtecan; T-DXd) Patient-reported outcomes in DESTINY-Breast11: neoadjuvant treatment with trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (ddAC-THP) in high-risk, HER2+ early-stage breast cancer S. Modi RF6-06 Rapid Fire 6 Mini-Oral Session Wednesday, December 10 1:00 – 2:00 pm DESTINY-Breast11 safety: neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (ddAC-THP) in high-risk, HER2+ early-stage breast cancer G. Curigliano RF6-02 Rapid Fire 6 Mini-Oral Session Wednesday, December 10 1:00 – 2:00 pm Additional efficacy and safety from the DESTINY-Breast05 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T‑DM1) in patients with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary early breast cancer with residual invasive disease after neoadjuvant therapy S. Loibl RF6-01 Rapid Fire 6 Mini-Oral Session Wednesday, December 10 1:00 – 2:00 pm Trastuzumab deruxtecan (T-DXd) + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) for first-line treatment of patients with HER2 positive (HER2+) advanced/metastatic breast cancer: patient-reported outcomes from the DESTINY-Breast09 study M. Rimawi RF6-07 Rapid Fire 6 Mini-Oral Session Wednesday, December 10 1:00 – 2:00 pm Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer: final analysis from DESTINY-Breast03 S. Im PS5-01-30 Poster Session 5 Friday, December 12 12:30 – 2:00 pm Trastuzumab deruxtecan (T-DXd) monotherapy and T-DXd + pertuzumab in patients with previously untreated HER2+ unresectable/metastatic breast cancer: final results from DESTINY-Breast07 F. Andre PS5-01-14 Poster Session 5 Friday, December 12 12:30 – 2:00 pm Outcomes by hormone receptor status in patients with HER2+ advanced/metastatic breast cancer with brain metastases treated with trastuzumab deruxtecan (T-DXd): a post-hoc subgroup analysis of DESTINY-Breast12 H. Wildiers PS5-01-27 Poster Session 5 Friday, December 12 12:30 – 2:00 pm DESTINY-Breast Respond HER2 low Europe: description of first enrolled patients in the non-interventional study of T-DXd in HER2 low metastatic breast cancer V. Guarneri PS5-08-14 Poster Session 5 Friday, December 12 12:30 – 2:00 pm Interim analysis results for the effectiveness and safety of trastuzumab deruxtecan in patients with HER2 low breast cancer and brain metastases: the HALLOW study N. Niikura PD13-11 Poster Spotlight 13 Friday, December 12 7:00 – 8:30 am Translational analysis of cerebrospinal fluid and plasma circulating tumor DNA from breast cancer patients with leptomeningeal disease treated with trastuzumab deruxtecan (T-DXd) in the DEBBRAH trial A. Fitzpatrick PS2-08-20 Poster Session 2 Wednesday, December 10 5:00 – 6:30 pm Trials-in-Progress A randomized phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus CDK4/6 inhibitor-based endocrine therapy as first-line therapy of hormone receptor-positive and HER2 low/ultralow advanced breast cancer patients classified as non-luminal subtype according to gene expression profiling: the PONTIAC study J. Cortes PS5-07-15 Poster Session 5 Friday, December 12 12:30 – 2:00 pm Phase 1b study of EZH1/2 inhibitor valemetostat in combination with trastuzumab deruxtecan in subjects with HER2 low/ultralow/null metastatic breast cancer S. Damodaran PS5-09-22 Poster Session 5 Friday, December 12 12:30 – 2:00 pm DATROWAY (datopotamab deruxtecan; Dato-DXd) First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) for whom immunotherapy was not an option: additional safety analyses from the TROPION-Breast02 study T. Traina PS5-03-05 Poster Session 5 Friday, December 12 12:30 – 2:00 pm Intracranial activity of datopotamab deruxtecan (Dato-DXd) for patients with HER2 negative breast cancer and leptomeningeal disease: results from cohort C of the DATO-Base phase 2 trial P. Tarantino PS1-09-02 Poster Session 1 Wednesday, December 10 12:30 – 2:00 pm Trials-in-Progress TROPION-Breast06: multicenter, multinational, open-label, single-arm, phase 3b study of datopotamab deruxtecan (Dato-DXd) in patients with locally advanced inoperable or metastatic HR+/HER2 IHC 0 breast cancer refractory to endocrine therapy K. Jhaveri PS5-07-21 Poster Session 5 Friday, December 12 12:30 – 2:30 pm Patritumab Deruxtecan (HER3-DXd) Outcome of patritumab deruxtecan (HER3-DXd) in patients with HER2 positive metastatic breast cancer and CNS involvement previously treated with T-DXd: a subanalysis of TUXEDO-3 R. Bartsch PD13-10 Poster Spotlight 13 Friday, December 12 7:00 – 8:30 am Trials-in-Progress HERTHENA-Breast04: a phase 3, randomized, open-label study evaluating the efficacy and safety of patritumab deruxtecan (HER3-DXd) versus treatment of physician’s choice in hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) unresectable locally advanced or metastatic breast cancer B. Pistilli PS5-07-22 Poster Session 5 Friday, December 12 12:30 – 2:00 pm HERTHENA-Breast03: a phase 2, randomized, open-label study evaluating neoadjuvant patritumab deruxtecan (HER3-DXd) + pembrolizumab before or after pembrolizumab + chemotherapy for early-stage TNBC or HR-low+/HER2− breast cancer J. O’Shaughnessy PS5-12-21 Poster Session 5 Friday, December 12 12:30 – 2:00 pm HERTHENA-Breast01: a phase 1b/2, multicenter, open-label, dose-finding study to evaluate the safety and antitumor activity of patritumab deruxtecan (HER3-DXd) in HER2+ unresectable locally advanced or metastatic breast cancer S. Tolaney PS5-12-23 Poster Session 5 Friday, December 12 12:30 – 2:00 pm 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 six 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 is being developed by Daiichi Sankyo. Additional ADCs being developed by Daiichi Sankyo include DS-9606, which consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload and DS3610, which consists of an antibody attached to a novel immunomodulatory payload that acts as an agonist of STING. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS-9606 and DS3610 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.