Approximately 95% of colorectal cancers are classified as microsatellite stable (MSS) and have historically been unresponsive to immunotherapy. These patients lack effective options after developing resistance; standard care provides only a 1-2% response rate, with a median survival of 6-7 months.
According to a study presented at the 2023 ASCO Gastrointestinal Cancer Symposium, the combination therapy of Botensilimab and Balstilimab can provide durable efficacy for patients with refractory, metastatic, microsatellite stable colorectal cancer.
Botensilimab is an Fc-enhanced CTLA-4 inhibitor, and Balstilimab is a PD-1 inhibitor. Researchers tested the efficacy of this combination therapy in a phase 1 trial.
Extended data from the Phase 1b C-800 study showed that dual immunotherapy with the CTLA-4 monoclonal antibody Botensilimab and the PD-1 monoclonal antibody Balstilimab induced deep objective responses in patients with heavily pretreated MSS-type metastatic colorectal cancer (mCRC), with evidence of durability and encouraging tolerability.
On April 17, 2023, Agenus Inc., an immuno-oncology company, received Fast Track designation from the U.S. Food and Drug Administration (FDA) for investigation of the combination of botensilimab (AGEN1181) and balstilimab (AGEN2034). This designation is for patients with metastatic colorectal cancer who are not microsatellite highly unstable (MSI-H)/mismatch repair deficient (dMMR) and who do not have active liver involvement.
Regarding safety, most patients reported treatment-related adverse reactions. Common adverse reactions included diarrhea/colitis and fatigue. Common grade 3 adverse reactions included diarrhea/colitis, fatigue, and fever.
The company is conducting a global randomized phase 2 trial comparing botensilimab in combination with balstilimab versus standard of care in patients with non-microsatellite high instability (non-MSI-H) colorectal cancer.
