LEXINGTON, Mass. — Agenus Inc. said Phase 1b data for its botensilimab and balstilimab combination in patients with treatment-refractory hepatocellular carcinoma were published in the journal Liver Cancer.
The Lexington-based immuno-oncology company said the study evaluated botensilimab, an Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab, an anti-PD-1 antibody, in patients whose hepatocellular carcinoma had progressed after prior immunotherapy.
The publication reported results from an expansion cohort of the Phase 1b C-800-01 study involving 19 patients. Agenus said the cohort represented a difficult-to-treat population, including patients with poorer liver reserve and prognosis. Forty-seven percent of patients had albumin-bilirubin grade 2 liver function.
Among 18 efficacy-evaluable patients, the combination showed an objective response rate of 17%, including one complete response and two partial responses. The 18-week clinical benefit rate was 50%. Median duration of response was not reached, median progression-free survival was 4.4 months and median overall survival was 12.3 months.
All patients had received prior anti-PD-(L)1 therapy, while 68% had received prior tyrosine kinase inhibitors and 58% had received prior atezolizumab and bevacizumab. One patient had stable disease for 66 weeks.
“This publication adds to a consistent body of clinical evidence showing BOT plus BAL activity across difficult-to-treat, late-line solid tumors,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “In HCC, where tumor biology and underlying liver function both shape treatment outcomes, these data further support the rationale for botensilimab’s Fc-enhanced CTLA-4 design and its potential to drive immune activity in settings where conventional checkpoint approaches have had limited impact.”
Anthony B. El-Khoueiry, M.D., chief of the Section of Developmental Therapeutics and associate director for clinical research at USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC, and principal investigator of the study, said patients with advanced hepatocellular carcinoma who progress after immunotherapy have limited treatment options.
“Patients with advanced HCC who progress after immunotherapy have limited treatment options, and outcomes can be especially poor when liver function is compromised,” El-Khoueiry said. “In this exploratory cohort, seeing objective responses, prolonged disease control and a median overall survival of 12.3 months is encouraging and supports continued study of BOT plus BAL in this post-immunotherapy setting.”
Agenus said the safety profile of the combination in the liver cancer cohort was consistent with prior reports across the broader Phase 1b program. There were no treatment-related deaths and no new class safety signals. Immune-mediated treatment-related adverse events occurred in 68% of patients, with grade 3 events in 37%. No grade 4 or higher immune-mediated treatment-related adverse events were reported.
The C-800-01 trial is an open-label, multicenter Phase 1b study evaluating botensilimab in combination with or without balstilimab in patients with advanced solid tumors. The HCC expansion cohort enrolled 19 patients between March 2021 and September 2023 across six U.S. sites.
