Ifinatamab deruxtecan

TOKYO, Japan & BASKING RIDGE, NJ, USA I September 23, 2024 I Topline results from the TROPION-Breast01 phase 3 trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy, which previously met the dual primary endpoint of progression-free survival (PFS), did not achieve statistical significance in the final overall survival (OS) analysis in patients with inoperable or metastatic hormone receptor (HR) positive, HER2 low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). This analysis follows the positive PFS results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS. An improvement in patient-reported outcomes was also seen. 1 The PFS data and additional results for key secondary endpoints were published this month in the Journal of Clinical Oncology . The safety profile of datopotamab deruxtecan was consistent with that observed in the previous analysis, including lower rates of grade 3 or higher treatment-related adverse events compared to chemotherapy, and no new safety concerns identified. All grade interstitial lung disease (ILD) rates remained low with no new grade 3 or higher ILD events observed. With ADCs approved during the course of the trial, including ENHERTU ® (trastuzumab deruxtecan), subsequent treatment following patients’ disease progression or treatment discontinuation is likely to have affected survival results. “Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with ENHERTU and we remain committed to making datopotamab deruxtecan another potential option for patients who can benefit.” “The metastatic HR positive breast cancer treatment landscape has advanced remarkably in the last several years to the benefit of patients,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting. We will continue discussions with regulatory authorities and apply insights from these results to our clinical development program for datopotamab deruxtecan in breast cancer.” The data will be presented at an upcoming medical meeting and shared with regulatory authorities currently reviewing applications for this indication. In addition to TROPION-Breast01, Daiichi Sankyo and AstraZeneca are evaluating datopotamab deruxtecan alone and with immunotherapy as treatment for patients with triple negative or HR low, HER2 negative breast cancers in the TROPION-Breast02 , TROPION-Breast03 , TROPION-Breast04 and TROPION-Breast05 phase 3 trials. About TROPION-Breast01 TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR positive, HER2 low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease. Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted. The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov . About Hormone Receptor Positive Breast Cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 2 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally. 2 While survival rates are high for those diagnosed with early breast cancer, less than 35% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 3 Approximately 70% of diagnosed cases are considered what has been historically called HR positive, HER2 negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-). 3 Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer. 4 However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited. 4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 4,5,6,7 TROP2 is a protein broadly expressed in HR positive, HER2 negative breast cancer and is associated with increased tumor progression and poor survival. 8,9 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including non-small cell lung cancer, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. 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 datopotamab deruxtecan (Dato-DXd) 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 datopotamab deruxtecan. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 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 for the treatment of adult patients with: 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 Pernas S, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer: Patient-reported outcomes (PROs) from the TROPION-Breast01 study. Presented at: ASCO Congress 2024; 31 May – 4 June, 2024; Chicago, IL. Abstract 1006. 2 Bray F, et al. CA Cancer J Clin . 2024; 10.3322/caac.21834. 3 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes . Accessed September 2024. 4 Manohar P, et al. Cancer Biol Med . 2022 Feb 15; 19(2):202–212. 5 Cortes J, et al. Lancet . 2011;377:914-923. 6 Yuan P, et al. Eur J Cancer . 2019;112:57-65. 7 Jerusalem G, et al. JAMA Oncol . 2018;4(10):1367–1374. 8 Goldenberg D, et al. Oncotarget . 2018;9(48): 28989-29006. 9 Vidula N, et al. Breast Cancer Res Treat . 2022 Aug;194(3):569-575. SOURCE: Daiichi Sankyo

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。 9月17日，Merck和第一三共宣布其ADC药物patritumab deruxtecan（HER3-DXd）已通过了3期HERTHENA-Lung 02研究。在今年的ESMO会议结束几个月后，该药物因生产问题被美国FDA拒之门外。根据公布的结果，两家公司将与全球监管单位就该试验结果进行进一步的讨论。 Patritumab deruxtecan是一款采用第一三共技术设计的潜在first-in-class靶向HER3的DXd ADC，目前正由第一三共公司和Merck联合开发。 HERTHENA-Lung02 3期试验评估了patritumab deruxtecan（HER3-DXd）对既往接受过EGFR酪氨酸激酶抑制剂（TKI）治疗的局部晚期或转移性表皮生长因子受体突变非小细胞肺癌（NSCLC）患者的治疗效果，该试验达到了无进展生存期（PFS）的主要终点，与铂类加培美曲塞诱导化疗及后续培美曲塞维持疗法相比，PFS有显著的统计学改善。在进行分析时，总生存期（OS）数据尚不成熟，该试验将继续进一步评估次要终点OS。 HERTHENA-Lung02的安全性与在之前肺癌临床试验中的安全性一致，没有发现新的安全性信号。大多数间质性肺病（ILD）事件级别较低（1级和2级）。观察到两例5级间质性肺病事件（表面患者已死亡），在其第2阶段研究中也曾发现了一例5级 ILD 病例。 这项合作开始于2023年10月，第一三共和默沙东就第一三共的三款ADC候选药物：patritumab deruxtecan（HER3-DXd）、ifinatamab deruxtecan（I-DXd）和raludotatug deruxtecan（R-DXd）达成了全球开发和商业化协议，将在全球范围内共同开发和潜在商业化这些候选ADC疗法。第一三共将保留日本的独家权利。第一三共将全权负责产品生产和供应。 根据协议，ifinatamab deruxtecan项目默沙东将向第一三共支付15亿美元的预付款；patritumab deruxtecan项目和raludotatug deruxtecan项目的预付款分别也是15亿美元。根据某些销售里程碑的实现情况，默沙东还将为每个项目支付额外的55亿美元里程金。结合其他合作条款，三个项目的潜在交易总价值高达220亿美元。 2024年8月6日，第一三共与默沙东共同宣布扩大了现有的三项研究性DXd抗体偶联药物的全球共同开发和共同商业化协议，将默克公司的MK-6070（一种研究性δ样配体3 (DLL3)靶向T细胞结合器）纳入其中。这款药物是默沙东此前斥资约6.8亿美元收购Harpoon Therapeutics获得的。 根据协议，默沙东将获得1.7亿美元预付款，以及根据销售额收取一定的特许权使用费，两家公司将在全球（除日本）共同开发和商业化 MK-6070，默沙东将保留该药物在日本的独家代理权。此外，默沙东负责MK-6070的生产和供应，并记录该产品的全球销售额。与MK-6070和ifinatamab deruxtecan联合使用相关的研发费用将按照ifinatmab deruxtecan的原始协议进行分摊。 今年6月26日，FDA拒批了第一三共和默沙东提交的加速批准Patritumab Deruxtecan（HER3-DXd）的生物制品许可申请（BLA），CRL指出原因是在第三方制造设施的检查发现问题，并未指出申请中提交的功效或安全性数据存在任何问题。第一三共表示将与FDA和第三方制造商密切合作，尽快解决反馈问题。 参考资料：公司官网