Botensilimab Plus Balstilimab Demonstrates Promise in Refractory Metastatic Colorectal Cancer

Key Clinical Summary:

• Design/Population: A systematic comparative analysis reconstructed patient-level data from a phase 1 trial of botensilimab plus balstilimab and compared outcomes with 4 pivotal trials (SUNLIGHT, FRESCO-2, RECOURSE, and CORRECT) in unselected patients with refractory microsatellite-stable metastatic colorectal cancer.
• Key Outcomes: Botensilimab plus balstilimab demonstrated improved overall survival vs standard therapies (regorafenib/trifluridine-tipiracil plus bevacizumab, fruquintinib, regorafenib, and trifluridine and tipiracil monotherapy). Progression-free survival improvements were observed vs most comparators, although trifluridine-tipiracil plus bevacizumab showed superior progression-free survival. The regimen had a distinct safety profile, with fatigue and diarrhea as the most common adverse events.
• Clinical Relevance: Dual checkpoint blockade with botensilimab plus balstilimab shows promising survival benefit in refractory microsatellite-stable metastatic colorectal cancer, a historically immunotherapy-resistant population, supporting further randomized evaluation to define its role relative to current standards.

According to a comparative analysis of clinical trial data, botensilimab plus balstilimab improved overall survival (OS) compared with current standard therapies among patients with refractory microsatellite-stable metastatic colorectal cancer (mCRC). 

“Over the past year, many early phase trials evaluating novel compounds have been designed [and] promising results have been reported with the combination of botensilimab [plus] balstilimab,” stated Elisabetta Bengala, MD, Regina Elena National Cancer Institute, Rome, Italy, and coauthors. “We carried out a systematic review of clinical trials of unselected patients with refractory mCRC, with the aim of comparing new treatment strategies with the current standard of care.” 

Researchers collected data from a phase 1 study of botensilimab plus balstilimab and 4 pivotal trials in refractory mCRC (SUNLIGHT, FRESCO-2, RECOURSE, and CORRECT). Individual patient-level OS and progression-free survival (PFS) data were reconstructed from Kaplan-Meier curves, and safety profiles were compared across treatment regimens. The primary end point was OS. Key secondary end points included PFS and safety. 

At analysis, botensilimab plus balstilimab improved median OS compared with regorafenib and trifluridine and tipiracil plus bevacizumab (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44 to 0.89) and also outperformed later-line standard therapies, including fruquintinib (HR, 0.38) regorafenib (HR, 0.32) and trifluridine-tipiracil monotherapy (HR, 0.37).

Improvements in PFS were also observed compared with most standard treatments however, trifluridine and tipiracil plus bevacizumab demonstrated superior PFS compared with botensilimab plus balstilimab (HR, 0.46).

The safety profile of botensilimab plus balstilimab differed from that of cytotoxic and targeted therapies and was associated with fatigue and diarrhea as the most common adverse events. Standard regimens were associated with hematologic toxicities, nausea, hypertension, and dermatologic adverse effects.

 “By comparing current standard-of-care treatments with a potential novel therapy in refractory mCRC, this review underscores existing gaps and highlights future research priorities while awaiting randomized data,” concluded Dr Bengala et al. 

Source:

Bengala E, Santini D, Picone V. Refractory microsatellite-stable metastatic colorectal cancer: A comparison between botensilimab + balstilimab and current standard of care. IOTECH. Published online: November 27, 2025. doi:10.1016/j.iotech.2025.101558