PO.CT01.05 · 临床试验

S2302-PRAGMATICA-LUNG的最终结果：一项在既往接受免疫治疗的IV期或复发性非小细胞肺癌（NSCLC）受试者（pts）中比较ramucirumab联合pembrolizumab（RP）与标准治疗（SOC）的前瞻性随机研究

Final Results from S2302-PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (RP) versus standard of care (SOC) for participants (pts) previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC)

编号 CT140 展板 4 时间 4/20 02:00–05:00 区域 Section 52 主讲 Karen Reckamp, MD;MS

分会场 Phase II and Phase III Clinical Trials

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作者与单位 Authors & Affiliations

Karen L. Reckamp¹, Mary W. Redman², Konstantin H. Dragnev³, Maya Khalil⁴, Brian S. Henick⁵, James Moon², Pasarlai Ahmadzai⁶, Michael LeBlanc², Daniel R. Carrizosa⁷, Paul J. Hesketh⁸, Ellen V. Sigal⁹, Jeff Allen⁹, Andreas N. Saltos¹⁰, Bryan A. Faller¹¹, Roy S. Herbst¹², Charles D. Blanke¹³, Jhanelle E. Gray¹⁰

¹Cedars-Sinai Medical Center, Los Angeles, CA,²SWOG Statistics and Data Management Center; Fred Hutchinson Cancer Center, Seattle, WA,³Dartmouth Cancer Center, Lebanon, NH,⁴The University of Alabama, Birmingham, Birmingham, AL,⁵Columbia University/Herbert Irving Comprehensive Cancer Center, New York, NY,⁶Cancer Research and Biostatistics, Seattle, WA,⁷Levine Cancer Institute/ Wake Forest Baptist Comprehensive Cancer Center, Charlotte, NC,⁸Lahey Hospital and Medical Center, Burlington, MA,⁹Friends of Cancer Research, Washington, DC,¹⁰Moffitt Cancer Center, Tampa, FL,¹¹Heartland NCORP/Missouri Baptist Medical Center, St. Louis, MO,¹²Yale University, New Haven, CT,¹³SWOG Network Operations Center/Oregon Health & Science University, Portland, OR

摘要 Abstract

中文摘要

背景：在一线免疫检查点抑制剂（ICI）为基础的治疗之后，晚期NSCLC可用的有效治疗选择很少。随机II期Lung-MAP S1800A研究比较RP与SOC用于既往接受ICI治疗的NSCLC患者，证明了总生存期（OS）获益且毒性谱优于SOC。SWOG S2302 Pragmatica-Lung采用务实设计，在评估OS的同时增加试验参与的代表性。中期分析此前已报告。方法：S2302是一项以注册为目的的随机III期试验，针对既往至少84天接受ICI以及铂类为基础治疗的晚期NSCLC患者，随机分配至SOC或RP，按紧邻的既往治疗（包括ICI[是/否]）和PS（0/1对2）分层。务实设计使入选标准聚焦于分期、既往治疗和安全性。不要求实验室评估和影像学检查。主要目标为OS。次要目标为比较各组间关键亚组（包括鳞状细胞癌[SCC]）内的OS，并总结严重和意外的高级别治疗相关AEs报告。入组目标为800例，基于使用单侧2.5%水平对数秩检验对HR 0.77的90%效能。完全信息为616例OS事件。结果：S2302于2023年3月至2024年12月入组838例患者，每组419例。研究数据在无效性中期分析时公布。中位年龄（范围）为68岁（34-88），22%非白种人/13%黑人，15%农村，29% SCC，63%腺癌，81%以ICI作为最近治疗，13%为PS2。在报告的582例死亡中，各组间OS无差异（HR 1.04 [0.88-1.22] p=0.66；RP的中位OS[mOS]为10.1个月[mos]，SOC为10.0 mos）。在SCC中，HR（95% CI）为0.90 [0.66-1.22] p=0.25，RP的mOS为10.7 mos，SOC为9.6 mos。在非SCC中，HR（95% CI）为1.10 [0.91-1.34] p=0.84，RP的mOS为9.8 mos，SOC为10.6 mos。结论：务实的试验设计带来了快速入组和更高的受试者代表性。RP总体上未改善OS，但不劣于SOC。值得注意的是，对于SCC，估计HR<1且置信区间符合非劣效性界值。我们的解读是，对于SCC，RP可能提供一种与SOC等效但耐受性更好的选择。资助：NIH/NCI/NCTN基金U10CA180888和U10CA180819；部分由Merck Sharp & Dohme LLC（Merck & Co., Inc.的子公司，美国新泽西州Rahway）和Eli Lilly and Company支持。

查看英文原文 English abstract

Background: Few effective treatment options for advanced NSCLC are available following frontline immune checkpoint inhibitor (ICI)-based therapy. The randomized, phase II Lung-MAP S1800A study of RP versus SOC for pts with NSCLC previously treated with ICI demonstrated benefit in overall survival (OS) with an improved toxicity profile over SOC. SWOG S2302 Pragmatica-Lung was pragmatically designed to evaluate OS while increasing representation in trial participation. The interim analysis was previously reported. Methods: S2302 is a registration-intent randomized phase III trial for pts with advanced NSCLC who previously received ICI for at least 84 days and platinum-based therapy, randomized to SOC or RP, stratified by immediate prior therapy including ICI (yes/no) and PS (0/1 v. 2). The pragmatic design led to eligibility focused on stage, prior therapy and safety. Laboratory assessment and imaging were not required. The primary objective was OS. The secondary objectives were to compare OS between the arms within key subgroups, including squamous cell carcinoma (SCC) and to summarize reports of serious and unexpected high-grade treatment-related AEs. The accrual goal was 800 based on 90% power for an HR of 0.77 using a 1-sided 2.5% level log-rank test. Full information was 616 OS events. Results: S2302 enrolled 838 pts with 419 in each arm from March 2023 to December 2024. Study data were released at an interim analysis for futility. Median age (range) was 68 (34-88), 22% non-white /13% Black, 15% rural, 29% SCC, 63% adenocarcinoma, 81% had ICI as the most recent treatment, 13% had PS2. With 582 deaths reported, OS was not different between the arms (HR 1.04 [0.88-1.22] p= 0.66; median OS (mOS) was 10.1 months (mos) for RP and 10.0 mos for SOC). In SCC, the HR (95% CI) was 0.90 [0.66-1.22] p= 0.25 with mOS of 10.7 mos for RP and 9.6 mos with SOC. In nonSCC, the HR (95% CI) was 1.10 [0.91-1.34] p= 0.84 with mOS of 9.8 mos for RP and 10.6 mos with SOC. Conclusions: The pragmatic trial design led to rapid accrual with increased participant representativeness. RP did not improve OS overall but was not worse than SOC. Of note, for SCC, the estimated HR is < 1 and the confidence interval is consistent with non-inferiority bounds. We interpret that RP for SCC may provide an option equivalent to SOC with better tolerability. Support: NIH/NCI/NCTN grants U10CA180888 and U10CA180819; and in part by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Eli Lilly and Company

利益披露 Disclosure

K. L. Reckamp, AstraZeneca Independent Contractor. Genentech Independent Contractor, ). GlaxoSmithKline Independent Contractor. Immunity Bio Independent Contractor. Johnson & Johnson Independent Contractor, ). Lilly Independent Contractor. Merus Independent Contractor. Novartis Independent Contractor. Nuvation Independent Contractor. Pfizer Independent Contractor. BioNTech ). Blueprint ). Daiichi Sankyo ). Elevation Oncology ). M. W. Redman, None. K. H. Dragnev, Amgen ). Daiichi Sankyo/Astra Zeneca ). G1 Therapeutics ). Io Therapeutics ). Lilly ). Merck ). Molecular Templates ). Novartis ). Roche/Genentech ). M. Khalil, Abbvie ). Advenchen Laboratories ). Amgen ). Arcus Biosciences ). Artios ). Astellas Pharma ). AstraZeneca ). BeiGene ). Black Diamond Therapeutics ). Boehringer Ingelheim ). Bristol-Myers Squibb Company ). Cantargia AB ). Caris Life Sciences ). DynamiCure Biotechnology ). Exelixis ). Genentech/Roche ). Guardant Health ). Henlius ). Johnson & Johnson/Janssen ). Kronos ), Research to institution, Lilly; Lucence; Merck; NGM Biopharmaceuticals; Nitto BioPharma; Numab; Orum Therapeutics; Relay Therapeutics; Seagen; Spectrum Pharmaceuticals; Taiho Pharma; Takeda; TopAlliance BioSciences; Xencor. B. S. Henick, AstraZeneca Independent Contractor. Bayer Independent Contractor. Boehringer Ingelheim Independent Contractor. Bristol-Myers Squibb Independent Contractor. Genentech/Roche Independent Contractor, ). IDEAYA Biosciences Independent Contractor. Jazz Pharmaceuticals Independent Contractor. Regeneron Independent Contractor. Sorrento Therapeutics Independent Contractor. Synthekine Independent Contractor. Johnson & Johnson/Janssen ). NexImmune ). J. Moon, None.. P. Ahmadzai, None. M. LeBlanc, Agios Independent Contractor. D. R. Carrizosa, Coherus Biosciences Independent Contractor. Curio Science Independent Contractor. Targeted Oncology Independent Contractor. Bristol Myers Squibb Independent Contractor. OncLive/MJH Life Sciences Independent Contractor. PER Independent Contractor. Elevation Oncology ). Merck ). Scorpion Therapeutics ). Takeda ). P. J. Hesketh, UpToDate Independent Contractor. E. V. Sigal, EQRx Independent Contractor, Stock. GRAIL Independent Contractor, Stock. AstraZeneca Travel. J. Allen, None. A. N. Saltos, AstraZeneca ). MJH Life Sciences Independent Contractor. Bayer Independent Contractor. Boehringer Ingelheim Independent Contractor. Daiichi Sankyo/Astra Zeneca Independent Contractor, ). Janssen Independent Contractor, ). Lilly Independent Contractor, ). Pfizer Independent Contractor. DAVA Oncology Travel. Genentech ). BioAtla ). Genmab ). Memgen ). Mersana ). NGM Biopharmaceuticals ). Novartis ). Turning Point Therapeutics ). B. A. Faller, Amgen Travel. AstraZeneca Travel. Boehringer Ingelheim Travel. Celgene Travel. EB SQUIBB Travel. Eisai Travel. Genentech Travel. Lilly Travel. Merck Travel. Novartis Travel. Takeda Travel. R. S. Herbst, Junshi Pharmaceuticals g., Board of Directors, non-salaried role), Independent Contractor. American Association for Cancer Research g., Board of Directors, non-salaried role). Friends of Cancer Research g., Board of Directors, non-salaried role). IASLC g., Board of Directors, non-salaried role), Travel. Immunocore g., Board of Directors, non-salaried role), Stock. Society for Immunotherapy of Cancer g., Board of Directors, non-salaried role). SWOG g., Board of Directors, non-salaried role), Travel. Bolt Biotherapeutics; Checkpoint Therapeutics; Normunity Independent Contractor, Stock. American Cancer Society Travel. AstraZeneca; Genentech/Roche; Lilly; Merck Independent Contractor, ). Abbvie Independent Contractor. Amgen Independent Contractor. ArriVent Biopharma Independent Contractor. Bristol-Myers Squibb Independent Contractor. Candel Therapeutics Independent Contractor. Catalym Independent Contractor. Cybrexa Therapeutics Independent Contractor. Gilead/Forty Seven Independent Contractor. I-Mab Independent Contractor. Janssen Independent Contractor, Independent contractor: Mediflix; NEUVOGEN; NextCure; Novartis; Pfizer; Regeneron; Sanofi. C. D. Blanke, None. J. E. Gray, Abbvie Independent Contractor, Travel. AstraZeneca Independent Contractor, ). Blueprint Medicies Independent Contractor. Daiichi Sankyo Independent Contractor. EMD Serono/Merck Independent Contractor, ). Flatiron Health Independent Contractor. Gilead Sciences Independent Contractor, ). IDEOlogy Health Independent Contractor. Janssen Independent Contractor. Jazz Pharmaceuticals Independent Contractor. Merck Independent Contractor, ). Novartis Independent Contractor, ). OncoCyte Independent Contractor, Travel. Pfizer Independent Contractor, ). Regeneron Independent Contractor, ). Spectrum ODAC Independent Contractor, Travel. Takeda Independent Contractor. Triptych Health Partners Independent Contractor. Array BioPharma ). Boehringer Ingelheim ), Research funding to institution: Bristol-Myers Squibb; G1 Therapeutics; Genentech; Lilly; Ludwig Institute for Cancer Research; Panbela Therapeutics.

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