Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial.
Publication Title
Nature medicine
Document Type
Article
Publication Date
6-13-2024
Keywords
oregon; portland; chiles; california; santa monica
Abstract
Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study. The primary endpoint is safety and tolerability, which was evaluated separately in the dose-escalation portion of the study and in patients with MSS mCRC (using combined dose-escalation/dose-expansion data). Secondary endpoints include investigator-assessed RECIST version 1.1-confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS). Here we present outcomes in 148 heavily pre-treated patients with MSS mCRC (six from the dose-escalation cohort; 142 from the dose-expansion cohort) treated with BOT and BAL, 101 of whom were considered response evaluable with at least 6 months of follow-up. Treatment-related adverse events (TRAEs) occurred in 89% of patients with MSS mCRC (131/148), most commonly fatigue (35%, 52/148), diarrhea (32%, 47/148) and pyrexia (24%, 36/148), with no grade 5 TRAEs reported and a 12% discontinuation rate due to a TRAE (18/148; data fully mature). In the response-evaluable population (n = 101), ORR was 17% (17/101; 95% confidence interval (CI), 10-26%), and DCR was 61% (62/101; 95% CI, 51-71%). Median DOR was not reached (NR; 95% CI, 5.7 months-NR), and median PFS was 3.5 months (95% CI, 2.7-4.1 months), at a median follow-up of 10.3 months (range, 0.5-42.6 months; data continuing to mature). The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with durable responses. ClinicalTrials.gov identifier: NCT03860272 .
Clinical Institute
Digestive Health
Clinical Institute
Cancer
Specialty
Gastroenterology
Specialty
Oncology
DOI
10.1038/s41591-024-03083-7
Recommended Citation
Bullock, Andrea J; Schlechter, Benjamin L; Fakih, Marwan G; Tsimberidou, Apostolia M; Grossman, Joseph E; Gordon, Michael S; Wilky, Breelyn A; Pimentel, Agustin; Mahadevan, Daruka; Balmanoukian, Ani S; Sanborn, Rachel E; Schwartz, Gary K; Abou-Alfa, Ghassan K; Segal, Neil H; Bockorny, Bruno; Moser, Justin C; Sharma, Sunil; Patel, Jaymin M; Wu, Wei; Chand, Dhan; Rosenthal, Katherine; Mednick, Gabriel; Delepine, Chloe; Curiel, Tyler J; Stebbing, Justin; Lenz, Heinz-Josef; O'Day, Steven J; and El-Khoueiry, Anthony B, "Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial." (2024). Articles, Abstracts, and Reports. 9029.
https://digitalcommons.providence.org/publications/9029
10.1038/s41591-024-03083-7