Dr Fakih on the Future of Botensilimab and Balstilimab–Based Therapies in MSS mCRC

"Now that we know the recommended dose to move forward [with for the combination of botensilimab and balstilimab], we're hoping to see this go into a registrational trial comparing this combination to the current standard of care for third-line [MSS mCRC].”

Marwan Fakih, MD, a professor in the Department of Medical Oncology & Therapeutics Research and division chief of GI Medical Oncology at City of Hope, discusses the advancement of the combination of botensilimab and balstilimab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) following early-phase clinical trial results presented at the 2025 Gastrointestinal Cancers Symposium.

Findings from a phase 2 trial (NCT05608044) presented at the meeting showed that at a median follow-up of 12.7 months (range, 1.6-19.7), patients with refractory MSS mCRC who received botensilimab at 75 mg every 6 weeks in combination with balstilimab at 240 mg once every 2 weeks (n = 62) achieved a confirmed ORR (ORR) of 19% (95% CI, 10%-31%) and a disease control rate (DCR) of 55% (95% CI, 42%-68%). When botensilimab was administered at 150 mg every 6 weeks in combination with balstilimab (n = 61), the confirmed ORR was 8% (95% CI, 3%-18%) at a median follow-up of 12.9 months (range, 0.1-20.6) with a DCR of 54% (95% CI, 41%-67%). In the control arm, where patients (n = 33) received standard-of-care therapy with trifluridine/tipiracil (Lonsurf) or regorfenib (Stivarga), the confirmed ORR and DCR were 0% (95% CI, 0%-9%) and 36% (95% CI, 20%-55%), respectively, at a median follow-up of 10.9 months (range, 0.0-17.7).

A phase 3 trial further evaluating the combination of botensilimab and balstilimab in patients with refractory MSS mCRC could launch in 2025, Fakih explains.

Additionally, findings from a phase 1 trial (NCT05627635) presented at the meeting demonstrated that the combination of botensilimab, balstilimab, FOLFOX, and bevacizumab (Avastin) resulted in an objective response rate (ORR) of 71% in 14 patients with MSS metastatic CRC. In 12 patients who had received 1 to 2 prior lines of therapy, the ORR was 66%. The regimen was well tolerated, with only 1 patient requiring immune suppression for colitis and hepatitis, Fakih explains.

Fakih concludes that botensilimab/balstilimab continues to establish itself as a promising immunotherapeutic backbone for MSS mCRC with the potential to enhance treatment efficacy when combined with additional agents, including systemic chemotherapy. Ongoing future studies will aim to refine dosing strategies and evaluate its potential integration into earlier lines of therapy.