Agenus Inc. (Nasdaq: AGEN) reported three-year overall survival data from its Phase Ib C-800-01 trial at ESMO GI 2026 in Munich, showing that 33% of patients with refractory microsatellite-stable (MSS) metastatic colorectal cancer without active liver metastases were alive at 36 months — a landmark in a disease setting where immunotherapy has historically produced no durable benefit and where approved later-line therapies have reported median overall survival of approximately 10–14 months. The three-year overall survival colorectal cancer figure, drawn from a fully enrolled 123-patient cohort, arrives as the company's Phase III BATTMAN trial is actively enrolling and as Agenus pursues regulatory submissions in the US and EU. The question the data must now answer is whether a single-arm Phase Ib readout carries sufficient weight to support approval before a randomized Phase III result is available.
MSS metastatic colorectal cancer accounts for approximately 95% of metastatic CRC cases and has historically been resistant to checkpoint inhibition because of its low mutational burden and limited T-cell infiltration. Conventional PD-1/CTLA-4 combinations such as nivolumab plus ipilimumab have shown little activity in this setting.
Botensilimab aims to overcome this resistance through enhanced Fc-receptor engagement that promotes depletion of intratumoral regulatory T cells. Combined with the anti-PD-1 antibody balstilimab, the regimen is designed to generate immune responses in tumors that have remained largely refractory to immunotherapy.
The updated data, presented by Dr. Benjamin Schlechter of Dana-Farber Cancer Institute, showed a median overall survival of 21.2 months, with 24-month and 36-month survival rates of 41% and 33%, respectively. Confirmed objective response rate was 21%, including three complete responses, while median duration of response was not reached, with responses lasting from 1.9 months to at least 37.4 months. Notably, 21 patients (17%) were alive and off all systemic anticancer therapy at last follow-up, including several who had remained free from subsequent treatment or death for more than two years, contributing to a Kaplan-Meier survival plateau rarely observed in this setting.
Patients had received a median of three prior lines of therapy, including approved later-line agents such as regorafenib, trifluridine/tipiracil and fruquintinib. Activity was maintained in the most heavily pretreated patients: among 37 individuals previously exposed to all available later-line therapies, confirmed objective response rate was 22%, median overall survival was 16.2 months, and the three-year overall survival rate reached 30%. Although cross-trial comparisons should be interpreted cautiously, the survival profile substantially exceeds historical outcomes reported with currently approved therapies for refractory MSS metastatic colorectal cancer.
Competitive context
The MSS mCRC immunotherapy space has attracted multiple approaches, and the competitive landscape has shifted materially in the past year. Exelixis's zanzalintinib in combination with Roche's Tecentriq (atezolizumab) demonstrated a statistically significant 20% reduction in risk of death versus regorafenib in the Phase III STELLAR-303 trial, with median OS of 10.9 months versus 9.4 months — a modest absolute benefit that nonetheless secured a positive primary endpoint in a randomized study. Exelixis has filed for US FDA approval. While the randomized Phase III data provide a stronger regulatory foundation, the magnitude and durability of benefit reported by Agenus appear greater, albeit from an uncontrolled study.