Agenus has announced groundbreaking results from a clinical trial, published in Nature Medicine, showcasing the potential of a novel immunotherapy combination for treating microsatellite stable metastatic colorectal cancer (MSS mCRC), a type of cancer typically resistant to immunotherapy. This research, led by international oncologists, evaluates the efficacy and safety of botensilimab (BOT), an Fc-enhanced anti-CTLA-4 antibody, combined with balstilimab (BAL), an anti-PD-1 antibody, to activate the immune system against this challenging cancer type.
Colorectal cancer is the second leading cause of cancer death in the United States. Although overall death rates from colorectal cancer (CRC) have declined, survival rates for advanced disease remain poor, with a rising incidence in younger populations. For the 95% of patients diagnosed with MSS mCRC, no approved immunotherapies exist, making long-term survival exceedingly rare.
Publication Highlights:
- Patient Group: The Phase 1 trial assessed 148 heavily pretreated MSS mCRC patients treated with the combination at active doses. This included 101 patients with long-term follow-up, of which 77 did not have active liver metastases as of November 29, 2023.
- Safety and Tolerability: No treatment-related deaths were reported, and side effects were manageable and consistent with other immunotherapies.
- Efficacy Results: In the 77 patients without active liver metastases, the Objective Response Rate (ORR) was 22% (17/77) with most responses ongoing, during a median follow-up of 13 months.
- Long-term Benefits: Durable responses were observed in patients without active liver metastases, with a median Duration of Response (DOR) not yet reached, and 69% of patients alive at one year.
As of March 1, 2024, updated results showed an increased ORR of 23% 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 Overall Survival (OS) rates were 71% and 62%, respectively, with a median OS of 21.2 months. The most common side effects included immune-related diarrhea or colitis, managed with standard therapies.
Clinical Implications:
This research highlights the potential of BOT and BAL as a significant advancement in the immunotherapy landscape for MSS mCRC, the most common type of colorectal cancer with no approved immunotherapies.
Future Directions:
A randomized Phase 2 study to confirm the safety and efficacy of the BOT and BAL combination has completed enrollment and will be discussed with the U.S. Food and Drug Administration at an End-of-Phase 2 Meeting in July. A Phase 3 trial is planned to begin later this year.
Access the Full Publication:
The full study details can be accessed here.
About Nature Medicine:
Nature Medicine is a premier scientific journal publishing peer-reviewed research across all fields of science and technology. Only about 8% of submissions are accepted, underscoring the journal’s commitment to significant scientific discoveries.
About Botensilimab:
Botensilimab is a human Fc-enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. It extends immunotherapy benefits to “cold” tumors that respond poorly to standard treatments. Botensilimab has shown clinical responses across nine metastatic, late-line cancers, either alone or in combination with Agenus’ investigational PD-1 antibody, balstilimab. For more information, visit ClinicalTrials.gov using identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.
About Colorectal Cancer:
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, accounting for 8.3% of cancer-related deaths annually. Despite declining overall mortality rates, survival remains poor for advanced disease, with a growing impact on younger populations. From 1995 to 2019, the number of patients under 55 diagnosed with CRC nearly doubled.
About Agenus:
Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a broad pipeline of immunological agents. The company’s mission is to expand the patient population benefiting from cancer immunotherapy through combination approaches, utilizing a repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics), and adjuvants (through SaponiQx). Agenus is headquartered in Lexington, MA.
