Dr Fakih on Responses With Botensilimab Plus Balstilimab in MSS CRC

“The fact that the dose of botensilimab at 75 mg as monotherapy was not associated a [significant ORR], but [that this ORR increased to] 19% when we added balstilimab is proof of principle that we do need balstilimab [in this regimen]. That’s why one can now confidently say that we need the combination.”

Marwan G. Fakih, MD, professor, Department of Medical Oncology & Therapeutics Research, associate director, Clinical Sciences, medical director, Briskin Center for Clinical Research, division chief, GI Medical Oncology, and co-director, Gastrointestinal Cancer Program, City of Hope, discusses response rates with botensilimab (AGEN-1181) with or without balstilimab (AGEN-2034) in patients with microsatellite-stable (MSS) colorectal cancer (CRC).

A phase 2 trial (NCT05608044) examined the combination checkpoint inhibitor therapy in patients with microsatellite instability–high and MSS localized CRC with no liver metastases. Early findings presented at the 2025 ASCO Gastrointestinal Cancers Symposium showed that the addition of balstilimab to botensilimab improved the objective response rate (ORR) vs botensilimab alone, Fakih begins.

At a median follow-up of 12.7 months (range, 1.6-19.7), patients with MSS disease who received botensilimab at 75 mg every 6 weeks in combination with balstilimab (n = 62) achieved a confirmed ORR (cORR) of 19% (95% CI, 10%-31%) and a disease control rate (DCR) of 55% (95% CI, 42%-68%), he reports. When botensilimab was administered at 150 mg every 6 weeks in combination withbalstilimab (n = 61), the cORR 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 monotherapy cohorts, botensilimab at 75 mg every 6 weeks (n = 38) and 150 mg every 6 weeks (n = 40) resulted in cORRs of 0% (95% CI, 0%-9%) and 8% (95% CI, 2%-20%), respectively. The corresponding DCRs were 37% (95% CI, 22%-54%) and 38% (95% CI, 23%-54%). The median follow-up in these cohorts was 9.8 months (range, 0.6-17.7) and 13.4 months (range, 0.7-21.1), respectively.

The median duration of response has not yet been reached, and 70% of responses remain ongoing, he notes. The lack of response with 75 mg of botensilimab as monotherapy, but the 19% cORR observed with the addition of balstilimab, supports the necessity of combination therapy to achieve optimal disease control, Fakih emphasizes. Based on the safety and efficacy data observed in this study, botensilimab at 75 mg every 6 weeks combined with balstilimab at 240 mg has been selected as the recommended dose for a phase 3 trial, he concludes.