A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer

作者：Elena Garralda, Ammar W. Sukari, Nehal J. Lakhani, Akash Patnaik, Yiyun Lou, Seock‐Ah Im, Talia Golan, Ravit Geva, Martin Wermke, M. de Miguel, J. Palcza, S. Jha, Marya F. Chaney, Anson K. Abraham, Jasmine Healy, Gerald Steven Falchook · 发表于：ESMO Open · 年份：2022 · DOI：10.1016/j.esmoop.2022.100639 · 被引用次数：99 · 研究领域：Cancer Immunotherapy and Biomarkers、Colorectal Cancer Treatments and Studies、Colorectal and Anal Carcinomas

BACKGROUND: Treatment options are limited for participants with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that progressed after two or more prior therapies. Studies have shown that blockade of both lymphocyte-activation gene 3 (LAG-3) and programmed cell death protein 1 (PD-1) can improve antitumor activity. Here, we evaluate the antitumor activity of the LAG-3 antibody favezelimab alone or in combination with pembrolizumab in participants with MSS mCRC. PATIENTS AND METHODS: Eligible participants with MSS PD-1/programmed death-ligand 1 (PD-L1) treatment-naive mCRC that progressed on two or more prior therapies received 800 mg favezelimab, 800 mg favezelimab plus 200 mg pembrolizumab, or 800 mg favezelimab/200 mg pembrolizumab co-formulation, every 3 weeks. The primary endpoint was safety, the secondary endpoint was objective response rate (ORR), and exploratory endpoints included duration of response, progression-free survival (PFS), and overall survival (OS). RESULTS: At the data cut-off date of 23 October 2020, a total of 20 participants received favezelimab alone, 89 received favezelimab plus pembrolizumab (including as favezelimab/pembrolizumab co-formulation); 48 had PD-L1 combined positive score (CPS) ≥1 tumors. At this interim analysis median follow-up was 5.8 months with favezelimab and 6.2 with favezelimab plus pembrolizumab. Treatment-related adverse events (TRAEs) were 65% with favezelimab and 65.2% with favezelimab plus pembrolizumab. Grade ...