Efficacy of Botensilimab, Balstilimab in Microsatellite Stable Metastatic Colorectal Cancer

For patients with microsatellite stable colorectal cancer (MSS CRC), treatment with inside-out (I-O) combinations has not proven to be effective in metastatic sites of disease beyond the lungs and lymph nodes, including in non-liver metastases (NLM) groups.

A study from Marwan Fakih, MD, and colleagues presented at the 2024 American Society of Clinical Oncology Annual Meeting analyzed the efficacy of the Fc-enhanced, multifunctional, anti–CTLA-4 antibody botensilimab plus balstilimab to treatment patients with MSS CRC.

Researchers evaluated the data of 77 patients with NLM MSS CRC who received botensilimab 1 or 2 mg/kg every 6 weeks and balstilimab 3 mg/kg every 2 weeks. The study’s primary end points included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS).

Following analysis, the ORR was 22% (n=17), the DCR was 73% (n=56), and the median DOR was not reached (95% CI, 5.7-not reached).

A subgroup analysis demonstrated that botensilimab and balstilimab resulted in comparable activity from metastatic sites beyond the lungs. Dr. Fakih and colleagues noted that 1 patient with an occult brain metastasis reported pseudoprogression, which was followed by a complete systemic response to treatment in target lung lesions.

Researchers found no new safety signals.

“In summary, for MSS CRC, botensilimab and balstilimab are differentiated from previous I-O combinations by producing deep and durable responses even in difficult-to-treat metastatic sites,” investigators wrote. “In NLM patients, responses were observed in 18% to 33% of sites of disease, including the peritoneum, soft tissue, pleura, and the brain. These compelling results support further investigation in the fully enrolled, randomized, global phase 2 trial in MSS CRC and a planned global phase 3 trial.”