Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial.

Autor: Bullock AJ; Beth Israel Deaconess Medical Center, Boston, MA, USA., Schlechter BL; Dana-Farber Cancer Institute, Boston, MA, USA., Fakih MG; City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Tsimberidou AM; The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Grossman JE; Agenus, Inc., Lexington, MA, USA., Gordon MS; HonorHealth Research Institute, Scottsdale, AZ, USA., Wilky BA; University of Colorado Cancer Center, Aurora, CO, USA., Pimentel A; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA., Mahadevan D; The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA., Balmanoukian AS; The Angeles Clinic and Research Institute, Los Angeles, CA, USA., Sanborn RE; Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA., Schwartz GK; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA., Abou-Alfa GK; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Medical College at Cornell University, New York, NY, USA.; Trinity College Dublin, Dublin, Ireland., Segal NH; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Medical College at Cornell University, New York, NY, USA., Bockorny B; Beth Israel Deaconess Medical Center, Boston, MA, USA., Moser JC; HonorHealth Research Institute, Scottsdale, AZ, USA., Sharma S; HonorHealth Research Institute, Scottsdale, AZ, USA., Patel JM; Agenus, Inc., Lexington, MA, USA., Wu W; Agenus, Inc., Lexington, MA, USA., Chand D; Agenus, Inc., Lexington, MA, USA., Rosenthal K; Agenus, Inc., Lexington, MA, USA., Mednick G; Agenus, Inc., Lexington, MA, USA., Delepine C; Agenus, Inc., Lexington, MA, USA., Curiel TJ; Dartmouth Cancer Center, Lebanon, NH, USA., Stebbing J; Anglia Ruskin University, Cambridge, UK. justin.stebbing@aru.ac.uk., Lenz HJ; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., O'Day SJ; Agenus, Inc., Lexington, MA, USA.; Providence Saint John's Cancer Institute, Santa Monica, CA, USA., El-Khoueiry AB; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA. elkhouei@med.usc.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2024 Sep; Vol. 30 (9), pp. 2558-2567. Date of Electronic Publication: 2024 Jun 13.
DOI: 10.1038/s41591-024-03083-7
Abstrakt: 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 .
(© 2024. The Author(s).)
Databáze: MEDLINE
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