Agenus Inc. (Nasdaq: AGEN) announced the peer-reviewed publication of mature Phase 1b clinical results evaluating the combination of botensilimab (BOT) and balstilimab (BAL) in patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases.

The study, published in Clinical Cancer Research, analyzed 123 heavily pretreated patients who had received a median of three prior lines of therapy. The combination demonstrated a median overall survival of 21.2 months and a three-year overall survival rate of 33%. Available later-line standard treatments have reported median overall survival of approximately 10 to 14 months in comparable patient populations.

The confirmed objective response rate was 21%, including three complete responses and 23 partial responses. Median duration of response was not reached, with responses extending to at least 37.4 months. Disease control rate was 69% at six weeks, and 17% of patients were alive and off all systemic anticancer therapy at last follow-up.

In an exploratory subgroup of 37 patients who had exhausted available later-line therapies, with a median of five prior lines of therapy, the combination showed a 22% objective response rate and median overall survival of 16.2 months, with a three-year overall survival rate of 30%.

Biomarker analyses showed responses in tumors with low tumor mutational burden and no detectable PD-L1 expression, and neither marker was associated with response in the evaluable population.

No new safety signals were observed with extended follow-up, and there were no treatment-related deaths. The most common immune-mediated adverse event, diarrhea and colitis, resolved in 98% of affected patients within a median of 14 days. Efficacy was consistent at both BOT dose levels of 1 mg/kg and 2 mg/kg, while lower rates of immune-mediated adverse events were observed at the 1 mg/kg dose.

Agenus said the findings support continued evaluation of BOT and BAL in the neoadjuvant setting, including a planned Phase 3 trial called ROBBIN in resectable MSS colon cancer.