Preliminary results from a randomized, open-label, phase 2 study of botensilimab (BOT) with or without balstilimab (BAL) in refractory microsatellite stable metastatic colorectal cancer with no liver metastases (MSS mCRC NLM).

作者：Marwan Fakih, Neil H. Segal, Benjamin L. Schlechter, Thierry André, Filippo Pietrantonio, Benny Johnson, Alexander Vasilyev, Smitha Krishnamurthi, Salvatore Siena, Wells A. Messersmith, Virgilio Souza E Silva, Andrew Scott Paulson, Elena Élez, Cathy Eng, Sabine Tejpar, Michel Ducreux, Wei Wu, Joseph E. Grossman, Eric Van Cutsem, Manuel Hidalgo · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.4_suppl.23 · 被引用次数：8 · 研究领域：Colorectal Cancer Treatments and Studies、Genetic factors in colorectal cancer、Cancer Genomics and Diagnostics

23 Background: BOT is an Fc-enhanced, multifunctional anti-CTLA−4 antibody designed to improve Fc gamma receptor-mediated effector functions and extend the reach of I-O to tumor types such as MSS mCRC. Here we present preliminary data from a randomized, open-label, phase 2 study in patients (pts) with MSS mCRC NLM treated with BOT ± BAL (anti-PD−1; NCT05608044). The study aimed to inform dose and contribution of components based on the primary endpoint of objective response rate (ORR) by RECIST 1.1 per investigator, and safety, and was not powered for statistical comparisons between arms. Methods: A total of 234 pts (intent-to-treat [ITT]) were randomized to BOT (up to 4 doses) 75 or 150 mg every 6 wks (Q6W), BOT 75 or 150 mg Q6W plus BAL 240 mg Q2W (up to 2 years), or standard of care (SOC; regorafenib or trifluridine/tipiracil). Results: Median age was 58 yrs (range 23—90), 50% male, 39% rectal, 44% 3L+, 43% ECOG 1, 58% KRAS mutant, 4% NRAS mutant, 83% prior bev, all MSS and/or pMMR by local testing. Key characteristics were well balanced with some exceptions including median time from diagnosis of metastatic disease to study entry (30 mos across arms; 45 mos SOC) and presence of peritoneal metastases (34% across arms; 42% 75 mg BOT / 240 mg BAL; 27% SOC). As of July 29, 2024, median follow-up was 9.8 mos. Key efficacy and safety data are shown (Table). Image based endpoints by blinded independent review, as well as overall survival will be reported in the future. Grade ≥3 ...