Dr Schlechter on the Safety of Botensilimab Plus Balstilimab in Pretreated MSS CRC

“The principal toxicity of botensilimab plus balstilimab is immune-related diarrhea/colitis. In this trial, we learned that early initiation of TNF inhibition is critical to the safety of patients and to keeping them on treatment.”

Benjamin L. Schlechter, MD, senior physician in the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discussed the safety profile of botensilimab in combination with balstilimab for the treatment of patients with refractory microsatellite-stable (MSS) metastatic colorectal cancer (CRC) without active liver metastases.

During the 2025 ESMO Gastrointestinal Cancers Congress, data from an updated analysis of the phase 2 C-800-01 trial (NCT03860272) showed that the most common any-grade immune-mediated adverse effect (imAE) with the combination in the overall population (n= 123) was diarrhea/colitis (41%), Schlechter began. Grade 3 diarrhea/colitis was reported in 15% of patients in the overall cohort. During the study, investigators learned that early initiation of treatment with tumor necrosis factor (TNF) inhibitors was key to enhancing patient safety and keeping patients on treatment, he added. TNF inhibitors such as infliximab (Remicade) are a steroid-sparing approach that maintains the beneficial immune response of the regimen, he concluded.

Additional safety data from C-800-01 revealed that any-grade imAEs occurred in 58% of patients in the overall population; 29% of these were grade 3 events. Beyond diarrhea/colitis, other common any-grade imAEs included immune thyroiditis (7%), pneumonitis (5%) hepatitis (5%), adrenal insufficiency (3%), and dermatologic events (3%). Other grade 3 AEs consisted of pneumonitis (2%), hepatitis (2%), adrenal insufficiency (2%), and dermatologic events (1%). Moreover, there was a low incidence of visceral toxicities outside of the gastrointestinal tract, only 1 imAE across the treatment cohorts, and no treatment-related deaths. The study authors concluded that the safety profile of botensilimab in combination with balstilimab was manageable in this patient population with no new safety signals.