Agenus publishes results from botensilimab trial in Nature Medicine

Agenus has published results from a clinical trial in Nature Medicine, revealing the potential of a novel immunotherapy combination for treating microsatellite stable metastatic colorectal cancer, a cancer type historically resistant to immunotherapy. This pioneering research, led by an international team of oncologists, focuses on the efficacy and safety of botensilimab, or BOT, an Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab, or BAL, an anti-PD-1 antibody. Together, these therapies are designed to activate the immune system against a cancer type historically resistant to immunotherapy. For the 95% of patients diagnosed with MSS mCRC, there are no approved immunotherapies, making long-term survival exceedingly rare. The Phase 1 trial assessed 148 heavily pretreated MSS mCRC patients treated with the combination at active doses; 101 of these with long term follow-up, and 77 of these without active liver metastases as of the data cutoff of November 29, 2023. There were no treatment related deaths in patients treated with the combination BOT/BAL, and side effects were manageable and consistent with immunotherapies. In the 77 patients without active liver metastases with a median follow-up of 13 months, the objective response rate, or ORR, was 22% and a majority of these responses were ongoing. Noteworthy are the durable responses observed in those without active liver metastases, with a median Duration of Response, or DOR, not yet reached and the majority of patients alive at one year. In a recent press release, Agenus disclosed updated results as of the data cutoff of March 1. At that time, the ORR had increased to 23% in the 77 patients, with a median follow up of 13.6 months. The median duration of response in the 18 responders was still not reached. The estimated 12-month and 18-month OS rates were 71% and 62%, respectively. The median OS was 21.2 months. The most common safety observations were immune-related diarrhea or colitis, which were managed in accordance with standard therapies. A randomized Phase 2 study to confirm the comparative safety and efficacy of the BOT and BAL combination has completed enrollment and will be included in an upcoming discussion with the FDA at a scheduled End-of-Phase 2 Meeting in July. A Phase 3 trial is planned to initiate later this year.