Results from a phase 1a/1b study of botensilimab (BOT), a novel innate/adaptive immune activator, plus balstilimab (BAL; anti-PD-1 antibody) in metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC).

作者：Anthony B. El-Khoueiry, Marwan Fakih, Michael S. Gordon, Apostolia Maria Tsimberidou, Andrea J. Bullock, Breelyn Ann Wilky, Jonathan C. Trent, Kim Allyson Margolin, Daruka Mahadevan, Ani Sarkis Balmanoukian, Rachel E. Sanborn, Gary K. Schwartz, Bruno Bockorny, Justin C. Moser, Joseph Elan Grossman, Waldo Ignacio Ortuzar Feliu, Katherine Rosenthal, Steven J O'Day, Heinz‐Josef Lenz, Benjamin L. Schlechter · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.4_suppl.lba8 · 被引用次数：56 · 研究领域：Cancer Immunotherapy and Biomarkers、Colorectal Cancer Treatments and Studies、Cancer Genomics and Diagnostics

LBA8 Background: BOT promotes optimized T cell priming, activation and memory formation by strengthening antigen presenting cell/T cell co-engagement. As an Fc-enhanced next-generation anti–CTLA-4 antibody, BOT also promotes intratumoral regulatory T cell depletion and reduces complement fixation. We present results from patients with MSS CRC treated with BOT + BAL in an expanded phase 1a/1b study; NCT03860272. Methods: Patients (pts) with metastatic MSS CRC received BOT 1 or 2 mg/kg every 6 weeks (Q6W) + BAL 3 mg/kg every 2 weeks. Crossover from monotherapy to combination therapy was permitted (rescue) as well as fixed-dosing (150 mg BOT Q6W + 450 mg BAL every 3 weeks). Results: Fifty-nine combination pts were evaluable for efficacy/safety (treated as of 19 May 2022 with ≥1 Q6W imaging assessment), including one rescue and one fixed-dose pt. Median pt age was 57 (range, 25-83), 58% were female, and 76% received at least three prior lines of therapy including prior immunotherapy (34%). Median follow-up was 6.4 months (range, 1.6-29.5). In all pts, objective response rate (ORR) was 22% (95% CI, 12-35), disease control rate (DCR) was 73% (95% CI, 60-84), and median duration of response (DOR) was not reached (NR), with 9/13 responses ongoing. The 12-month overall survival (OS) rate was 61% (95% CI, 42-75), with median OS NR. Of the 13 responders, 9 had RAS mutations (7 KRAS, 2 NRAS), 0 had BRAF mutations, 0/10 had a TMB of ≥10 mutations/Mb, and 1/7 was PD-L1 positive (≥1% combin...