Agenus Announces Three-Year Phase 1b Data, BOT+BAL Shows 33% Survival Rate

Agenus announced three-year landmark Phase 1b data from the fully enrolled C-800-01 cohort evaluating botensilimab, an Fc-enhanced multifunctional anti-CTLA-4 antibody, plus balstilimab, an anti-PD-1 antibody, in patients with refractory microsatellite-stable metastatic colorectal cancer without active liver metastases. The data were presented at the European Society for Medical Oncology Gastrointestinal Cancers Congress 2026 on July 2 in Munich, Germany. BOT+BAL demonstrated clinically meaningful long-term survival in a heavily pretreated patient population with historically limited benefit from conventional immune checkpoint inhibitors and few durable treatment options after progression on standard therapies. With extended follow-up, median overall survival was 21.2 months and the three-year overall survival rate was 33%, with the Kaplan-Meier curve showing a plateau beyond two years. Available later-line standards in refractory MSS mCRC without active liver metastases have historically reported median overall survival of approximately 10-14 months in relevant analyses, reflecting a treatment setting in which few patients have historically remained alive at later landmark timepoints and pivotal studies have generally focused on median survival rather than mature 36-month overall survival outcomes.i In this context, the survival profile, curve plateau beyond two years, and proportion of patients alive and off systemic anticancer therapy support the durability of benefit observed with BOT+BAL in this fully enrolled 123-patient Phase 1b cohort. The data build on the two-year overall survival results presented by Dr. Benjamin L. Schlechter of Dana-Farber Cancer Institute at ESMO GI 2025 and reflect an additional year of follow-up from the same cohort. With longer follow-up, the dataset now includes 26 confirmed responses; median duration of response was not reached; and 21 patients, or 17%, were alive and off all systemic anticancer therapy at last follow-up, including 13 responders. The Phase 1b cohort included 123 patients with MSS mCRC without active liver metastases. Patients had received a median of three prior lines of therapy; 67% had received at least three prior lines, 15% had received prior anti-PD-(L)1 with or without anti-CTLA-4 therapy, and 30% had received at least one later-line regimen of regorafenib, trifluridine/tipiracil with or without bevacizumab, or fruquintinib. Key Efficacy Results: Median overall survival: 21.2 months, with 24-month and 36-month overall survival rates of 41% and 33%, respectively; Confirmed objective response rate: 21%, including three complete responses and 23 partial responses; Median duration of response: not reached; responses ranged from 1.9 months to at least 37.4 months; Disease control rate: 69% at six weeks; Clinical benefit rate: 28% at 24 weeks; Tumor regression: observed in more than 40% of patients; Treatment-free survival: 21 patients or 17%, were alive and off all systemic anticancer therapy, including 13 responders with a subset of patients remaining free from subsequent therapy or death for more than two years. In a post hoc late-line-exposed subgroup of 37 patients who had received at least one prior regimen of regorafenib, trifluridine/tipiracil with or without bevacizumab, or fruquintinib, BOT+BAL showed a confirmed objective response rate of 22%, median overall survival of 16.2 months, and a three-year overall survival rate of 30%. In this subgroup, median duration of response was 16.6 months, disease control rate was 70%, and clinical benefit rate at 24 weeks was 27%. With extended follow-up, no new safety signals were observed and there were no treatment-related deaths. Immune-mediated diarrhea/colitis resolved in 98% of affected patients, with a median time to resolution of 14 days from onset. Treatment-related immune-mediated diarrhea/colitis was the most common immune-mediated adverse event. The selected Phase 3 regimen of BOT 1 mg/kg plus BAL demonstrated improved tolerability, with lower rates of immune-mediated diarrhea/colitis than the 2 mg/kg regimen.