Zimberelimab

This is the first study to comprehensively interconnect clinical outcomes from patients receiving a HIF-2a inhibitor with peripheral biomarker changes and associated tumor biology HIF-2a inhibition with casdatifan resulted in deep and sustained suppression of the hormone erythropoietin in blood (serum EPO), which correlated with higher response rates and longer progression-free survival (PFS) A pooled analysis from four monotherapy cohorts (n=121) of the ARC-20 study showed that advanced kidney cancer patients treated with casdatifan lived beyond a year without cancer progression (median PFS of 12.2 months) despite multiple prior treatments with other standard regimens HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences, Inc. (NYSE: RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer and inflammatory and autoimmune diseases, today announced a publication in Nature describing new research from the ARC-20 study. The publication evaluated casdatifan, an investigational, small-molecule HIF-2a inhibitor, as a monotherapy in patients with metastatic clear cell renal cell carcinoma (ccRCC). It is the first study to comprehensively describe the relationship between HIF-2a inhibitor-associated changes in circulating serum EPO, tumor biology and corresponding clinical activity. The study showed that in ccRCC patients with HIF-2a-driven tumors, deeper suppression of HIF-2a-associated production of serum EPO correlated with clinical benefit, including higher response rates and longer PFS. “This is the first study to comprehensively assess the relationship between HIF-2a inhibitor-associated suppression of serum EPO production with tumor biology and clinical outcomes,” said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute, the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, and lead investigator of ARC-20. “These findings were elucidated in parallel with demonstrating the meaningful clinical benefit of casdatifan, an investigational, HIF-2a inhibitor in development for the treatment of kidney cancer. Patients treated with casdatifan had a median progression-free survival of over one year despite half of patients having progressed on three or more prior treatments with other standard therapies.” The data showed that casdatifan monotherapy resulted in deep and sustained suppression of serum EPO, further validating EPO as a biomarker of HIF-2a inhibition. Deep suppression of serum EPO was correlated with higher response rates and longer PFS. High HIF-2a activity, as determined by expression of key genes in the HIF-2a pathway and baseline tumor EPO levels (evaluated by RNA levels and tissue imaging), correlated with improved clinical outcomes during casdatifan treatment. Taken together, these measures consistently supported the same conclusion and provide strong evidence linking the biology of HIF-2a-driven tumors to patient outcomes with casdatifan. “The comprehensive translational work published in Nature validates EPO as a biomarker for HIF-2a suppression and correlates dramatic and sustained EPO suppression to durable response with monotherapy casdatifan,” said Richard Markus, M.D., Ph.D., chief medical officer at Arcus Biosciences. “We believe this new research provides unambiguous evidence that casdatifan is a best-in-class HIF-2a inhibitor, and we are rapidly advancing a comprehensive development strategy so that every ccRCC patient has the opportunity to benefit from casdatifan across each line of therapy.” Arcus’s holistic development strategy is intended to provide physicians and patients with: 1) a casdatifan-based TKI-sparing first-line treatment; 2) a casdatifan-based TKI-inclusive first-line regimen; 3) a second-line HIF-2a inhibitor treatment that builds on the second-line standard-of-care TKI, cabozantinib; and 4) a late-line therapy that has been clinically validated to also provide benefit in patients previously treated with a HIF-2a inhibitor-based therapy. This research focused on various cohorts of the ARC-20 platform study that evaluated casdatifan monotherapy in patients with metastatic ccRCC. Four monotherapy cohorts (n=121) were included, across doses of 50mg twice daily (BID), 50mg once daily (QD), 100mg QD (tablet) and 150mg QD. Most of the patients had progressed on at least two prior lines of therapy, including both an anti-PD-1 and a VEGFR TKI. The patient population was heavily pretreated; in the pooled analysis, more than half (55%) of patients received at least three prior lines of therapy, and more than one quarter (29%) had received at least four prior lines of therapy. Most patients (71%) had an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor of intermediate or poor. At the time of the data cutoff (DCO, August 15, 2025), casdatifan produced durable antitumor activity. In the 100mg QD tablet cohort, the confirmed objective response rate (cORR) was 35% and median PFS (mPFS) had not yet been reached, with 60% of patients remaining progression-free at 12 months. In the pooled analysis of all four monotherapy cohorts (n=121), cORR was 31% and mPFS was 12.2 months, with continued reductions in tumor size observed beyond 12 months of treatment. In a later analysis with a January 30, 2026 DCO, conducted after these results were submitted for publication, mPFS was 15.1 months in the 100mg QD cohort, the same dose and formulation being used in the ongoing PEAK-1 Phase 3 study. 100mg QD Tablet (Phase 3 dose) (n=31) Pooled Analysis (50mg BID, 50mg QD, 100mg QD, 150mg QD) (n=121) Efficacy Median Follow-Up 12.4 months 15.5 months Median PFS [95% CI] Not estimable [5.7,NE] 12.2 months [9.4,20.6] 12-month PFS [95% CI] 60% [40,75] 50% [41,59] 6-month PFS [95% CI] 67% [48,81] 63% [54,71] Confirmed ORR [95% CI] 35% (11) [19,55] 31% (38) [23,40] Confirmed BOR CR PR SD PD 0 35% (11) 48% (15) 10% (3) <1% (1) 31% (37) 50% (60) 17% (21) Median Time to Response 2.6 months 2.8 months Disease Control Rate [95% CI] 84% (26) [66,95] 81% (98) [73,88] BOR: best overall response; CI: confidence interval; CR: complete response; cORR: confirmed objective response rate; NE: not estimable; PD: progressive disease; PFS: progression-free survival; PR: partial response; SD: stable disease At the time of the August 2025 DCO, no unexpected safety signals were observed, and casdatifan had an acceptable and manageable safety profile across all doses. The most common class-effect events were anemia and hypoxia; across all four cohorts, no patients discontinued treatment due to anemia, and three patients (2%) discontinued due to hypoxia. 100mg QD Tablet (Phase 3 Dose) (n=32) Pooled Analysis (50mg BID, 50mg QD, 100mg QD, 150mg QD) (n=127) Safety Any Serious TEAEs 31% (10) 31% (39) Grade ≥3 TEAEs related to casdatifan Anemia 25% (8) 41% (52) Hypoxia 9% (3) 11% (14) TEAEs resulting in discontinuation 9% (3) 9% (11) Anemia 0 0% (0) Hypoxia 3% (1) 2% (3) TEAE: treatment-emergent adverse event About Casdatifan (AB521) Casdatifan is a small-molecule inhibitor of hypoxia-inducible factor 2-alpha (HIF-2a), a master switch that turns on hundreds of genes in response to low oxygen levels. In a majority of people with the most common form of kidney cancer (clear cell renal cell carcinoma), genetic anomalies result in the dysregulation of this master switch and transformation of normal kidney cells into cancerous ones. Casdatifan was designed to provide deep and durable inhibition of the HIF-2a pathway. Early clinical studies have shown high response rates and a low primary progression rate relative to clinical benchmarks, warranting further investigation in late-stage studies. Casdatifan, which is administered in pill form once daily, has a safety profile that allows it to be investigated in combination with other treatments. The casdatifan development strategy is designed to generate evidence needed to establish casdatifan as a backbone therapy so that every ccRCC patient has the opportunity to benefit from casdatifan across each line of therapy. In addition to partner-operationalized studies, including combinations with casdatifan and anti-PD-X/VEGF bispecifics, Arcus is investigating casdatifan across multiple cohorts in the ARC-20 platform study, alone and in combination with other potential new treatment options, including in: the first-line setting with cohorts evaluating casdatifan plus zimberelimab, an anti-PD-1 (ongoing); casdatifan plus zimberelimab and ipilimumab, an anti-CTLA-4 (ongoing); and casdatifan plus an anti-PD-1/VEGF bispecific (planned) the second-line setting with a cohort evaluating casdatifan plus cabozantinib, a TKI, in immunotherapy-experienced patients (ongoing) a cohort evaluating casdatifan plus a TKI, in HIF-2a inhibitor-experienced patients (planned) Arcus is also enrolling PEAK-1, the global Phase 3 study evaluating casdatifan plus cabozantinib versus cabozantinib in IO-experienced patients with metastatic ccRCC. Arcus expects to complete enrollment in PEAK-1 and to initiate a Phase 3 study in the first-line metastatic ccRCC setting by year-end 2026. 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. Taiho has development and commercial rights in Japan and other countries in Asia, excluding China. Arcus Biosciences holds full rights to casdatifan everywhere else globally. About Kidney Cancer 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 80,450 Americans will be diagnosed with kidney cancer in 2026. ccRCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for kidney cancer is high; for patients with advanced or late-stage metastatic kidney cancer, however, the five-year survival rate is only 19%. For metastatic kidney cancer, targeted drug therapies are one of the main treatment options. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules for the treatment of cancer and inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of its late-stage portfolio of first- and/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 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. Arcus Forward-Looking Statements This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, Arcus’s development strategy and plans for casdatifan across each line of therapy. All forward-looking statements involve known and unknown risks and uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ materially from those expressed or implied by the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, risks associated with: interim data not being a guarantee of future data and may not be replicated in other studies evaluating casdatifan, including the Phase 3 PEAK-1 study; the unexpected emergence of adverse events or other undesirable side effects with casdatifan; risks associated with manufacturing or supplying product for clinical trials evaluating casdatifan; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. Risks and uncertainties facing Arcus are described more fully in the “Risk Factors” section of Arcus’s most recent periodic report filed with the U.S. Securities and Exchange Commission (SEC) and in other filings that Arcus makes with the SEC from time to time, which are available at www.sec.gov. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Arcus disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release, except to the extent required by law. The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners.

编者按 2026年欧洲肿瘤内科学会胃肠道肿瘤大会（ESMO Gastrointestinal Cancers Congress）将于7月1日至4日在德国慕尼黑国际会议中心（ICM）盛大召开。作为消化道肿瘤领域最具影响力的学术盛会之一，本次大会汇聚了全球顶尖的临床研究者、肿瘤学专家和医药研发人员，将集中展示从早期筛查、生物标志物驱动治疗到系统治疗创新的最新进展。 目前，大会官网已公布了除Late-Breaking Abstract（LBA）外的全部入选研究摘要。本文梳理了本次大会最具分量的口头报告（Proffered Paper和Rapid Oral）核心内容，涵盖结直肠癌、肝胆肿瘤、胃食管癌和胰腺癌四大领域的前沿突破。 结直肠癌： 围术期策略优化与精准治疗并进 ATOMIC研究：辅助治疗时长再审视 ATOMIC研究（摘要号：1O）针对Ⅲ期dMMR结肠癌患者，探索阿替利珠单抗联合mFOLFOX6辅助治疗的持续时间是否影响疗效。 结果显示，只有完成≥6个周期（约3个月）化疗的患者，联合阿替利珠单抗才能显著获益（3年DFS率88.2% vs 79.1%；aHR 0.46），而化疗周期不足的患者未观察到DFS改善。值得关注的是，阿替利珠单抗治疗超过12个周期未带来额外的DFS获益（84.0% vs 88.0%；aHR 0.81），提示免疫辅助治疗并非“越长越好”。该研究为临床决策提供了精准的时间窗口参考。 GALAXY研究：ctDNA-MRD精准指导肝转移术后治疗 GALAXY研究（摘要号：8O）是本次大会备受瞩目的焦点之一。研究纳入298例结直肠癌肝转移（CLM）切除术后的患者，采用个体化肿瘤知情检测评估术后ctDNA-MRD状态。 关键发现具有直接临床转化价值： MRD阳性患者：接受辅助化疗较观察组显著改善OS（48个月OS率：65% vs 33%；HR 0.27）和DFS（48个月DFS率：38% vs 7%；HR 0.07）。 MRD阴性患者：辅助化疗无OS或DFS获益，长期预后良好（HR 0.54）。 ctDNA-MRD可精准筛选出能从辅助化疗中获益的患者，支持在直接手术的CLM患者中前瞻性验证ctDNA指导的辅助治疗策略。 TORCH-iTNT更新：免疫TNT在pMMR直肠癌中的疗效 中国学者章真教授团队报告的TORCH-iTNT研究（摘要号：295RO）评估了免疫治疗为基础的全程新辅助治疗（iTNT）在pMMR局部晚期直肠癌（LARC）中的疗效。 192例患者随机接受CAPOX+特瑞普利单抗（A组）或短程放疗后序贯CAPOX+特瑞普利单抗（B组）。结果显示，B组总体CR率显著优于A组（60.2% vs 37.3%），其中手术pCR率分别为43.4%和32.8%。这是首个比较两种iTNT方案在pMMR LARC中疗效的研究，为器官保留策略提供了新的证据。 其他亮点 KRAS G12C新药Calderasib：KANDLELIT-001研究（摘要号：6RO）报道了该药在KRAS G12C突变晚期CRC中的数据。 抗EGFR再挑战策略：5项RCT的个体患者数据分析（摘要号：4RO）为后线治疗提供了决策依据。 LBA3：中国学者宋章法教授报告的Ⅲ期研究，探索了改良短程放疗联合CAPOX及替雷利珠单抗在pMMR/MSS LARC中的应用。 肝胆肿瘤： TACE+靶免OS折戟，FGFR2抑制剂交出亮眼答卷 EMERALD-1：PFS获益未能转化为OS改善 EMERALD-1研究（摘要号：183O）是肝胆肿瘤领域的重磅研究。该Ⅲ期研究此前已达到主要终点——度伐利尤单抗+贝伐珠单抗+TACE相比单纯TACE显著改善了不可切除HCC患者的PFS（15.0个月 vs 8.2个月；HR 0.77）。 然而，本次报告的最终OS分析令人意外：D+B+TACE组中位OS为29.9个月，而TACE组为33.3个月（HR 1.10；P=0.470），未能转化为生存获益。D+TACE组OS同样无改善（33.6个月 vs 33.3个月；HR 0.93）。 这一结果提示，在TACE基础上加用免疫+抗血管治疗虽能延缓疾病进展，但需警惕长期暴露于联合治疗可能增加毒性负担，反而抵消了PFS获益。安全性数据显示D+B+TACE组3/4级治疗相关不良事件发生率高达27.3%，而TACE组仅为7.5%。 EMERALD-3研究（摘要号：LBA2）将在本次大会报告曲麦利尤单抗+度伐利尤单抗±仑伐替尼联合TACE的肿瘤缓解分析。 PROACTIF：钇-90真实世界剂量-生存数据 PROACTIF研究（摘要号：184RO）纳入989例HCC患者，聚焦巨大肿瘤和门静脉血栓（PVT）这一难治人群。 关键发现：高剂量（≥400Gy）显著改善OS，且与肿瘤大小无关。Vp1-Vp2期PVT患者接受≥200Gy和≥400Gy时，mOS与无PVT患者相似。Vp3期PVT患者接受≥400Gy剂量时呈现类似趋势。 结论：对于巨大病灶或PVT患者，靶向≥400Gy的肿瘤剂量是实现生存获益的必要条件。 Fanregratinib：FGFR2融合ICC的ORR达42.5% 中国学者徐建明教授报告的Ⅱ期研究（摘要号：343RO）评估了泛FGFR抑制剂Fanregratinib在既往经治FGFR2融合/重排肝内胆管癌（ICC）中的疗效。 87例患者接受Fanregratinib 300mg每日一次（2周用药/1周停药方案），独立审查委员会评估的客观缓解率（ORR）达42.5%（37/87；95%CI 32.0%~53.6%），疾病控制率83.9%，中位PFS 6.9个月，中位OS 16.6个月。该研究达到预设的有效性界值，为FGFR2融合ICC患者提供了新的治疗选择。 胰腺癌： KRAS G12D靶向联合方案带来突破曙光 胰腺癌领域有多项研究入选口头报告，其中最引人注目的是针对KRAS G12D这一难治靶点的联合策略。 Zoldonrasib + Daraxonrasib联合方案 摘要号341O报道了zoldonrasib（RMC-9805，G12D选择性抑制剂）联合daraxonrasib（RMC-6236，多靶点RAS抑制剂）在二线及以上KRAS G12D突变mPDAC中的I期数据。 60例患者接受联合治疗（中位随访12.2个月），初步疗效令人鼓舞：中位PFS和OS数据虽然尚未完全成熟，但已显示出超越现有化疗的潜力；安全性可控，≥3级TRAE主要为皮疹（12%）和贫血（10%）。 约40%的PDAC患者存在KRAS G12D突变，而目前尚无获批的靶向疗法。该联合方案已启动全球性Ⅱ期研究（RASolute 309），评估其在一线治疗中的疗效。 其他胰腺癌研究 Zoldonrasib联合化疗一线治疗（摘要号：340O）：同样值得关注。 CLDN18.2靶向药物佐妥昔单抗联合吉西他滨+白蛋白紫杉醇的Ⅱ期GLEAM研究（摘要号：342O）。 LBA4：TRIPP-FFX研究——磷-32微粒子瘤内植入联合FOLFIRINOX治疗局部晚期胰腺癌。 胃食管癌： 免疫联合、新靶点与生活质量并重 STAR-221：双免疫联合化疗挑战一线标准 摘要号493O报道了STAR-221 Ⅲ期研究——domvanalimab（抗TIGIT）+ zimberelimab（抗PD-1）+化疗对比纳武利尤单抗+化疗一线治疗HER2阴性晚期胃癌/胃食管结合部癌/食管腺癌。该研究有望重新定义一线治疗格局。 HERIZON-GEA-01：HER2阳性mGEA的HRQoL数据 摘要号494O和495RO分别报告了泽尼达妥单抗+化疗±替雷利珠单抗一线治疗HER2阳性晚期/转移性胃食管腺癌（mGEA）的健康相关生活质量（HRQoL）和缓解特征分析。在关注疗效的同时，患者生活质量的评估日益受到重视。 PD-L1检测方法学争议 摘要号496RO聚焦胃食管腺癌中PD-L1检测方法和评分方法的互换性问题（EORTC ASPIRE项目）。这一问题直接关系到免疫治疗患者的筛选和临床决策的一致性。 临床决策精准化： 生物标志物驱动治疗走向前台 2026年ESMO GI大会传递了消化道肿瘤领域的几个明确趋势： 精准分层指导治疗决策：ctDNA-MRD指导辅助化疗（GALAXY）、分子标志物筛选靶向人群（KRAS G12D，FGFR2，CLDN18.2），均体现了从“群体治疗”向“个体化治疗”的转变。 靶向KRAS的突破：从G12C到G12D，从单药到联合，RAS通路抑制在胰腺癌和结直肠癌中持续推进，有望填补巨大的未满足需求。 免疫治疗时机的精细化：ATOMIC研究表明“疗程不是越长越好”，提示未来需要建立基于biomarker的动态治疗时长策略。 局部治疗与系统治疗的整合：HCC领域TACE+靶免的OS折戟敲响警钟；而钇-90剂量优化和FGFR2抑制剂在胆管癌中的数据则提供了积极范例。 中国学者持续活跃：TORCH-iTNT（王雅琪）、Fanregratinib（徐建明）、LBA3（宋章法）等多项研究入选口头报告，体现了中国在消化道肿瘤临床研究领域的国际影响力。 随着LBA数据的陆续揭晓，ESMO GI 2026必将为消化道肿瘤的临床实践带来更多改变。我们拭目以待。 免责声明：本账号分享的内容仅为健康信息科普，不构成任何医疗建议。个人健康问题，请务必咨询执业医师。 编辑 | 佼娇 排版 | 粘洞 审核 | 晓娟 鹏哥 版权声明： 本文版权归医悦汇所有，欢迎转发分享！ 其他任何媒体如需转载或引用本网版权所有内容，须获得授权，且在醒目位置处注明 “ 转自：医悦汇 ”。