Patritumab Deruxtecan

TOKYO--(BUSINESS WIRE)--The Biologics License Application (BLA) seeking accelerated approval in the U.S. for Daiichi Sankyo (TSE: 4568) and Merck’s (NYSE: MRK), known as MSD outside of the United States and Canada, ifinatamab deruxtecan (I-DXd) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy has been voluntarily withdrawn. The decision to withdraw the BLA is based on discussions with the U.S. Food and Drug Administration (FDA) that data supporting the application, including from the IDeate-Lung01 phase 2 trial, do not satisfy requirements needed to support an accelerated approval for the proposed indication. The accelerated approval pathway in the U.S. allows for earlier approval of medicines based on surrogate endpoints to treat serious conditions where there is an unmet medical need. Patient enrollment continues in the IDeate-Lung02 phase 3 trial evaluating the efficacy and safety of ifinatamab deruxtecan versus treatment of physician’s choice of chemotherapy (amrubicin, lurbinectedin or topotecan) in patients with relapsed ES-SCLC following disease progression with only one prior line of 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. “Extensive-stage small cell lung cancer is a challenging disease to treat, leaving patients in need of new options,” said Abderrahmane Laadem, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo. “Enrollment into the IDeate-Lung02 phase 3 trial is near completion and we look forward to assessing the potential for a future filing of ifinatamab deruxtecan with the FDA and other global regulatory authorities based on those results.” “While we are disappointed that the current dataset are not supportive of an approval at this time, we are continuing to evaluate the role of ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer and other types of difficult-to-treat cancer,” said Marjorie Green, MD, Senior Vice President, Head of Oncology Global Clinical Development, Merck Research Laboratories. “We would like to thank the patients, their families and investigators who have participated or continue to participate in these studies.” In addition to the IDeate-Lung02 phase 3 trial, there are two additional phase 3 trials underway with ifinatamab deruxtecan in advanced/metastatic disease, including IDeate-Prostate01 for castration-resistant prostate cancer (CRPC) and IDeate-Esophageal01 for esophageal squamous cell carcinoma (ESCC). 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. Patients with a history of interstitial lung disease (ILD)/pneumonitis requiring treatment with steroids or current ILD/pneumonitis at screening, clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, were not eligible. 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 include duration of response, progression-free survival, disease control rate, time to response, overall survival, 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 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, CRPC and ESCC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. 12,13,14,15 About Ifinatamab Deruxtecan Ifinatamab deruxtecan is an investigational potential first-in-class B7-H3 directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, 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 has been granted Orphan Drug Designation (ODD) by the U.S. FDA, European Commission, Japan Ministry of Health, Labour and Welfare, South Korea Ministry of Food and Drug Safety 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 ), CRPC ( IDeate-Prostate01 ) and ESCC ( IDeate-Esophageal01 ). About the Daiichi Sankyo and Merck Collaboration 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 MSD will maintain exclusive rights. MSD will be solely responsible for manufacturing and supply for gocatamig. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of nine 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. DS-3939 and DS3790 are being developed by Daiichi Sankyo. Additional ADCs being developed by Daiichi Sankyo include DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING, and DS1025, which consists of a CD25 directed antibody attached to an immuno-oncology optimized cytotoxic payload. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610, DS3790 and DS1025 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 (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator, transforming the lives of people through its strength in science and technology. The company discovers and develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies to deliver practice-changing medicines to patients, healthcare professionals and society. For more information, please visit . REFERENCES: Wang Q, et al. Journal of Thoracic Oncology . 2023 Jan;18(1):31-46. National Cancer Institute. SEER Explorer. Cancer Stat Facts: Lung and Bronchus Cancer . Accessed September 2026. U.S. Centers for Disease Control and Prevention. United States Cancer Statistics. Types of Lung Cancer | U.S. Cancer Statistics | CDC . Accessed September 2026. Rudin CM, et al . Nat Rev Dis Primers . 2021;7(1):3. National Cancer Institute. SEER Explorer. Small cell carcinoma of the Lung and Bronchus: 5-year Relative Survival . Accessed September 2026. American Cancer Society. Treatment Choices for Small Cell Lung Cancer, by Stage . Accessed September 2026. Liu SV, et al. J Clin Oncol . 2021;39(6):619-30. Paz-Ares L, et al. ESMO Open . 2022;7(2):100408. von Pawel J, et al. J Clin Oncol . 2014; 32:4012-4019. Zhao B, et al. J Hematol Oncol . 2022;15(1):153. Janakiram M, et al. Immunol Rev . 2017;276(1):26-39. Qiu M-j, et al. Front. Oncol . 2021;11:600238. Picarda E, et al. Clin Cancer Res . 2016;22(14):3425-3431. Bendell JC, et al. J Clin Oncol . 2020;39(15 suppl 1). Abstract TPS3646. Kontos F, et al. Clin Cancer Res . 2021;27(5):1227-1235. Contacts MEDIA CONTACTS: Global: Jennifer Brennan jennifer.brennan@daiichisankyo.com +1 908 900 3183 (mobile) Japan: DS-PR_jp@daiichisankyo.com INVESTOR RELATIONS CONTACT: DaiichiSankyoIR_jp@daiichisankyo.com

2026年9月25日，第一三共与默沙东联合发表公告，称已自愿撤回其向美国FDA提交的生物制品许可申请（BLA）。该申请寻求对ifinatamab deruxtecan（I-DXd，一款在研B7-H3导向抗体偶联药物）予以加速批准，用于成人广泛期小细胞肺癌（ES‑SCLC）患者，且患者在铂类化疗期间或之后出现疾病进展。 撤回BLA的决定基于与第一三共和默沙东与美国食品药品监督管理局（FDA）的沟通；沟通结论是，支持该申请的数据（包括IDeate‑Lung01二期试验的数据）不能满足拟定适应症加速批准所需的要求。 IDeate‑Lung02三期试验仍在招募患者，该试验评估ifinatamab deruxtecan对比研究者选择的化疗（阿柔比星、卢比替定或托泊替康）的疗效与安全性，对象为既往仅接受一线铂类化疗后进展的复发性ES‑SCLC患者。 “广泛期小细胞肺癌治疗难度很大，患者仍亟需新选择，”第一三共肿瘤治疗领域开发负责人Abderrahmane Laadem医学博士表示，“IDeate‑Lung02三期试验入组已接近完成，我们期待基于该试验结果，评估未来向FDA及其他全球监管机构提交ifinatamab deruxtecan上市申请的可能性。” “尽管我们对现有数据集目前不足以支持批准感到失望，但我们仍在继续评估ifinatamab deruxtecan在广泛期小细胞肺癌及其他难治癌症类型中的作用，”默沙东研究实验室全球临床开发肿瘤学高级副总裁兼负责人Marjorie Green医学博士表示，“我们感谢曾参与或继续参与这些研究的患者、其家属及研究人员。” 除IDeate‑Lung02三期试验外，ifinatamab deruxtecan还有两项针对晚期/转移性疾病的三期试验正在进行，包括IDeate‑Prostate01（去势抵抗性前列腺癌，CRPC）和IDeate‑Esophageal01（食管鳞癌，ESCC）。关于ifinatamab deruxtecan ifinatamab deruxtecan是一款在研、有望成为“同类首创”的B7‑H3导向抗体偶联药物（ADC）。其采用第一三共自有DXd ADC技术构建，由人源化抗B7‑H3 IgG1单克隆抗体通过基于四肽的可裂解连接子，偶联多个I型拓扑异构酶抑制剂载荷（依沙替康衍生物DXd）组成。 ifinatamab deruxtecan已获美国FDA、欧盟委员会、日本厚生劳动省及台湾食品药物管理部门授予孤儿药资格（ODD），用于小细胞肺癌；FDA还就其用于食管癌授予ODD。 一项全面的全球临床开发计划正在开展，评估ifinatamab deruxtecan单药及联合其他抗癌药在多种肿瘤中的疗效与安全性。该计划目前包含三项晚期/转移性疾病三期试验，分别为SCLC（IDeate‑Lung02）、CRPC（IDeate‑Prostate01）和ESCC（IDeate‑Esophageal01）。关于IDeate‑Lung01 IDeate‑Lung01（ClinicalTrials.gov，NCT05280470）是一项全球、多中心、随机、开放标签的二期试验，分两部分，评估ifinatamab deruxtecan在ES‑SCLC患者中的安全性与疗效；入组患者既往至少接受一线铂类化疗、最多三线治疗。试验在亚洲、欧洲和北美共入组187例。无症状脑转移（未治疗或已治疗）患者可入组；有需激素治疗的ILD/肺炎史或筛选时存在ILD/肺炎、因合并肺部疾病导致临床严重肺功能受损者不可入组。 第一部分（剂量优化）按1:1随机给予ifinatamab deruxtecan 8或12 mg/kg，静脉输注，每3周一次。第二部分（剂量扩展）给予12 mg/kg，同等间隔。 主要终点为盲态独立中心审查（BICR）按RECIST v1.1评估的客观缓解率（ORR）。次要终点包括缓解持续时间（DoR）、无进展生存期（PFS）、疾病控制率（DCR）、至缓解时间、总生存期（OS）、药代动力学及安全性。颅内ORR由BICR评估，作为探索性分析。关于小细胞肺癌 全球每年约25万例小细胞肺癌（SCLC）新发。2025年美国约2.7万例SCLC新发，占所有肺癌约12%。SCLC侵袭性强、迅速进展至远处转移阶段，五年生存率较低。虽然晚期SCLC常规标准治疗可改善结局，但仍需更多后线治疗手段。关于B7‑H3 B7‑H3是属于B7家族的跨膜蛋白，可与含PD‑1在内的CD28家族受体结合。它在多种肿瘤（包括SCLC）中高表达，且高表达与不良预后相关，因此成为有前景的治疗靶点。目前尚无获批用于抗癌的B7‑H3导向药物。关于第一三共与默沙东合作 第一三共与默沙东于2023年10月达成全球合作，共同开发和商业化ifinatamab deruxtecan（I‑DXd）、raludotatug deruxtecan（R‑DXd）和patritumab deruxtecan（HER3‑DXd）；日本除外，日本由第一三共保留独家权利。第一三共负责生产和供应。2024年8月，全球共同开发及商业化协议扩展纳入gocatamig（MK‑6070/DS3280），双方在全球（日本除外，日本由默沙东保留独家权利）共同开发及商业化；默沙东负责gocatamig的生产和供 立即扫码加入药事纵横交流群