Preliminary Data Show the Potential of Balstilimab Plus Botensilimab in MSS mCRC

Marwan G. Fakih, MD, professor in the Department of Medical Oncology & Therapeutics Research, co-directs the Gastrointestinal Cancer Program at City of Hope Comprehensive Cancer Center, provides an overview of the study design, rationale, and findings from a phase 2 trial (NCT05608044) which evaluated balstilimab with botensilimab for the treatment of patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) without liver metastases. Fakih presented on the trial at the 2025 Gastrointestinal Cancers Symposium.

Transcription:

0:10 | We presented the results of a randomized phase 2 clinical trial of botensilimab and balstilimab in different combinations, either monotherapy or in combination, and we compared that to a standard-of-care arm. This is a 5-arm trial, multicenter, and the main purpose of this study was to answer the question: what does balstilimab, which is a PD-1 inhibitor, add to botensilimab, which is a CTLA-4 inhibitor?

0:53 | Number 2, we also tried to answer the question, is there an optimal dose with botensilimab in that? It is a randomized phase 2 clinical trial with 5 arms, and the study was in patients with metastatic colorectal cancer who have microsatellite stability and have progressed on prior standard chemotherapy.

1:14 | The main endpoint of this study was overall response rate. What we found is that botensilimab plus balstilimab was effective in substantially reducing the tumor burden in patients. The overall response rate was 19% in patients who received both botensilimab/balstilimab with botensilimab at 75 mg every 6 weeks for up to 4 doses, and balstilimab at 40 [intravenously] every 2 weeks for up to 2 years. This was the highest response rate in the 5 arms that we tested.

1:52 | We also found that the combination at the higher dose of botensilimab, 150 mg, was associated with responses, but that was a little lower at 8%. Interestingly, the disease control rate, which is the combination of objective response and stable disease, was similar for the combination arm. The main result is that the highest response rate is with the lower dose of botensilimab 75 mg in combination with balstilimab, and we also found that when we gave botensilimab alone at the same dose level of 75 mg, we did not see objective responses, which confirms the contribution of both agents, meaning that you do need both agents together to get the best outcome.

REFERENCE:

1. Fakih M, Segal NH, Schlechter BL, et al. Preliminary results from a randomized, open-label, phase 2 study of botensilimab (BOT) with or without balstilimab (BAL) in refractory microsatellite stable metastatic colorectal cancer with no liver metastases (MSS mCRC NLM). J Clin Oncol. 2025;43(suppl 4):23. doi:10.1200/JCO.2025.43.4_suppl.23