Casdatifan

Arcus Biosciences公司正凭借其口服HIF-2α抑制剂casdatifan的最新数据，试图在肾癌领域与默克公司（Merck & Co.）一较高下，期望这款药物能与默克公司已确立地位的Welireg（belzutifan）相抗衡。I/Ib期ARC-20研究正在测试casdatifan不同单药治疗组的效果，同时还纳入了一个队列，评估每日一次100毫克casdatifan联合每日一次Exelixis公司的酪氨酸激酶抑制剂Cabometyx（cabozantinib）对透明细胞肾细胞癌（ccRCC）患者的疗效。当地时间周日，在美国临床肿瘤学会（ASCO）年会上，该公司首次公布了联合疗法的相关数据。截至3月14日的数据截止日，24名先前接受过免疫治疗但病情进展的透明细胞肾细胞癌患者接受了疗效评估。Arcus公司表示，casdatifan联合Cabometyx治疗的确认总缓解率（ORR）达到46%，其中1名患者（4%）达到完全缓解，10名患者（42%）达到部分缓解。12名患者（50%）病情稳定，1名患者病情进展。据公司称，“绝大多数接受疗效评估的患者仍在持续接受治疗。”此次数据公布距Arcus公司透露合作伙伴吉列德科学公司（Gilead Sciences）决定放弃该药物的选择权仅过去三个多月。当时，Arcus公司还公布了ARC-20研究中的一些单药治疗数据，包括每日两次50毫克剂量组的中位无进展生存期（PFS）为9.7个月，而每日一次50毫克或100毫克剂量组的中位无进展生存期均未达到。“ARC-20研究中casdatifan联合cabozantinib的初步数据，已经超过了两种药物单独使用时的历史基准，也超过了在同一二线治疗环境中另一种HIF-2α抑制剂联合cabozantinib的疗效，”Arcus公司首席执行官特里·罗森（Terry Rosen）在周日公司发布的新闻稿中表示。Arcus公司的数据将与Welireg进行对比。Welireg是一种HIF-2α抑制剂，于2023年获批用于治疗既往接受过PD-1/PD-L1和VEGF靶向疗法治疗的晚期肾细胞癌患者。在默克公司的III期LITESPARK-005试验中，将Welireg与依维莫司进行比较，结果显示Welireg可使疾病进展或死亡风险降低25%，不过两个治疗组的中位无进展生存期均为5.6个月。与此同时，Arcus公司官员曾表示，安全性将是ASCO会议展示中“非常重要的一部分”。周日，该公司表示ARC-20研究的安全性可控，casdatifan和Cabometyx之间“没有明显的毒性重叠”。在42名接受安全性评估的患者中，贫血是casdatifan治疗导致的3级或以上治疗相关不良事件（TRAE）中最常见的一种。10名患者（24%）出现该副作用，其中4名（10%）需要减少剂量。缺氧（7%）和中性粒细胞计数减少（2%）是该药物的其他显著副作用。未出现与casdatifan相关的4级或5级不良事件。贫血同样是Cabometyx治疗导致的3级或以上治疗相关不良事件中最常见的一种，6名患者（14%）出现该副作用，其中1名（2%）需要减少剂量。低钠血症（7%）、高血压（5%）和中性粒细胞计数减少（5%）是该药物的其他主要3级或以上治疗相关不良事件。5名患者（12%）因疲劳需要减少剂量。此次数据公布之际，Arcus公司正准备在未来几周内启动III期PEAK-1试验，评估casdatifan联合Cabometyx与单独使用Cabometyx对既往接受过抗PD-1治疗的转移性透明细胞肾细胞癌患者的疗效。此外，Ib/III期eVOLVE-RCC02试验将评估casdatifan联合阿斯利康公司的抗PD-1/CTLA-4双特异性抗体volrustomig对一线透明细胞肾细胞癌患者的疗效。信息来源：FirstWord Pharma药事纵横投稿须知：稿费已上调，欢迎投稿

HAYWARD, CA, USA I June 01, 2025 I Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, today presented the first data for casdatifan plus cabozantinib in an oral presentation by Dr. Toni K. Choueiri, Dana-Farber Cancer Institute, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. “I was very encouraged to see that nearly half of patients had a confirmed response to the casdatifan plus cabozantinib combination despite short follow-up,” said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber, the Jerome and Nancy Kohlberg Chair and professor of medicine at Harvard Medical School, and lead investigator of ARC-20. “Casdatifan plus cabozantinib was well tolerated, and the safety profile was consistent with that of either agent alone, supporting their potential as a combination therapy. I look forward to enrolling patients into the PEAK-1 trial as soon as it is open.” “The initial data for casdatifan plus cabozantinib in the ARC-20 study have already exceeded the historic benchmarks for either agent alone, as well as that of another HIF-2a inhibitor plus cabozantinib in the same second-line setting,” said Terry Rosen, Ph.D., chief executive officer of Arcus. “These data serve as the proof of concept for PEAK-1, which will be initiated in the coming weeks and is designed to generate evidence to change the standard of care for people who have progressed on prior immunotherapy treatment.” ARC-20 is a Phase 1/1b dose-escalation and expansion study that includes a cohort evaluating once-daily 100mg of casdatifan plus 60mg of cabozantinib in patients with ccRCC who had progressed on prior immunotherapy. At the time of the data cutoff (DCO, March 14, 2025), 42 participants were evaluable for safety, and 24 reached at least 12 weeks of follow-up and were evaluable for efficacy. Among the safety-evaluable population (N=42), most participants (79%) had an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor of intermediate or poor. Nearly half (46%) of the efficacy-evaluable population (N=24) achieved a confirmed response per RECIST 1.1, and only one patient had primary progressive disease. The vast majority of the efficacy-evaluable population remains on treatment. In the safety-evaluable population, no unexpected safety risks were identified at the time of DCO, and casdatifan plus cabozantinib had an acceptable safety profile with no meaningful overlapping toxicity for the two drugs. Only two patients discontinued any drug, and no patients discontinued treatment with both drugs. The incidence of treatment-emergent adverse events (TEAEs) with casdatifan, particularly anemia and hypoxia, was similar to TEAEs observed with casdatifan monotherapy, and there were no casdatifan-related Grade 4 or 5 adverse events. The incidence of TEAEs associated with each drug was consistent with what is expected for each drug alone. A summary of the efficacy and safety results is below. Arcus is pursuing a broad development program in both the immuno-oncology (IO)-naive and post-IO settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. These studies include: Investors may dial in to the conference call at +1 404 975 4839 (local) or +1 833 470 1428 (toll-free) using Conference ID: 446724 on Monday, June 2, 2025, at 5:00 AM PT / 7:00 AM CT. Participants may also register for the call online using the following link: https://events.q4inc.com/attendee/154065244 . To access the live webcast and accompanying slide presentation, please visit the “Investors & Media” section of the Arcus Biosciences website at www.arcusbio.com . A replay will be available following the live event. About Casdatifan (AB521) Casdatifan is a small-molecule inhibitor of HIF-2a, a transcription factor responsible for activating multiple tumor growth pathways in hypoxic and pseudo-hypoxic tumor environments. By selectively binding HIF-2a, casdatifan is designed to shut down hypoxic oncogenesis and key oncogenic pathways, which leads to cancer cell death. Clear cell renal cell carcinoma is almost universally associated with HIF-2a dysregulation. Casdatifan is currently being evaluated in ARC-20, a Phase 1/1b study in renal cell carcinoma. Casdatifan is an investigational molecule. Approval from any regulatory authority for its use has not been received, and its safety and efficacy have not been established. About RCC According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 80,980 Americans will be diagnosed with kidney cancer in 2025. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 18%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination therapies for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including domvanalimab, an Fc-silent anti-TIGIT antibody being studied in combination with zimberelimab, an anti-PD-1 antibody, for upper gastrointestinal and non-small cell lung cancer, casdatifan, a HIF-2a inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com . SOURCE: Arcus Biosciences