A phase 2 study evaluating response and biomarkers in patients with microsatellite stable (MSS) advanced colorectal cancer (CRC) treated with nivolumab/relatlimab.

作者：Eric Scott Christenson, Jennifer N. Durham, Madelena Brancati, Heather Davis Bruning, Susan Petrie, Hao Wang, Jiayun Lu, Katherine M. Bever, Dan A. Laheru, Ana De Jesus‐Acosta, Ross C. Donehower, Michael J. Pishvaian, Nilofer Saba Azad, Qingfeng Zhu, Nicolas Jose Llosa, Franck Housseau, Robert A. Anders, Drew M. Pardoll, Dung Thi Le · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.3554 · 被引用次数：2 · 研究领域：Genetic factors in colorectal cancer、Colorectal Cancer Treatments and Studies、Colorectal Cancer Surgical Treatments

3554 Background: Lymphocyte-activation gene 3 (LAG-3) is an immunosuppressive signal, impairing T effector (Teff) activation. Pre-clinical studies suggest LAG-3 inhibition promotes anti-tumor immunity by enhancing Teff function. Correlative studies linked increased LAG-3 levels with reduced overall survival (OS) in CRC. These data prompted optimism that combined LAG-3/PD-1 inhibition might promote anti-tumor responses in MSS CRC. Methods: We conducted a phase 2 study of nivolumab (Nivo) (aPD1)/relatlimab (Rela) (aLAG3) in patients with previously treated advanced MSS CRC. This study enrolled patients onto 1 of 3 arms. Arms A and B used a Composite PD-L1 and acellular Mucin (CPM) score to define patients as CPM(+) in Arm A (CPM≥ 15%) and CPM(-) in Arm B (CPM< 15%). Patients in Arm A and B received Nivo 480mg/Rela 160mg IV q4 weeks. Arm C enrolled patients without biomarker selection who received Nivo 480mg/Rela 960mg or Rela 480mg/Nivo 480mg. The primary endpoint was objective response, and each arm was powered to detect an objective response rate (ORR) of ≥20%. Results: Fifty nine evaluable patients were enrolled (Arm A: 12, Arm B: 15, Arm C: 32). Patient characteristics and responses are outlined. Treatment was well tolerated with no new safety signals over aPD1 alone. Three (5%) patients achieved a partial response (PR), 6 (10%) stable disease (SD), and 50 with progression of disease (PD) as best response. The median progression-free survival was (Arm A: 2.2 mo., Arm B: 2.8...