TY - JOUR
T1 - Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer
T2 - a phase 1 trial
AU - Bullock, Andrea J.
AU - Schlechter, Benjamin L.
AU - Fakih, Marwan G.
AU - Tsimberidou, Apostolia M.
AU - Grossman, Joseph E.
AU - Gordon, Michael S.
AU - Wilky, Breelyn A.
AU - Pimentel, Agustin
AU - Mahadevan, Daruka
AU - Balmanoukian, Ani S.
AU - Sanborn, Rachel E.
AU - Schwartz, Gary K.
AU - Abou-Alfa, Ghassan K.
AU - Segal, Neil H.
AU - Bockorny, Bruno
AU - Moser, Justin C.
AU - Sharma, Sunil
AU - Patel, Jaymin M.
AU - Wu, Wei
AU - Chand, Dhan
AU - Rosenthal, Katherine
AU - Mednick, Gabriel
AU - Delepine, Chloe
AU - Curiel, Tyler J.
AU - Stebbing, Justin
AU - Lenz, Heinz Josef
AU - O’Day, Steven J.
AU - El-Khoueiry, Anthony B.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85195828037&partnerID=8YFLogxK
U2 - 10.1038/s41591-024-03083-7
DO - 10.1038/s41591-024-03083-7
M3 - Article
C2 - 38871975
AN - SCOPUS:85195828037
SN - 1078-8956
JO - Nature Medicine
JF - Nature Medicine
ER -