On June 13, 2024 Agenus reported that it has published results from a groundbreaking clinical trial in Nature Medicine, revealing the potential of a novel immunotherapy combination for treating microsatellite stable metastatic colorectal cancer (MSS mCRC), a cancer type historically resistant to immunotherapy (Press release, Agenus, JUN 13, 2024, View Source [SID1234644314]). This pioneering research, led by an international team of oncologists, focuses on the efficacy and safety of botensilimab (BOT), an Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab (BAL), an anti-PD-1 antibody. Together, these therapies are designed to activate the immune system against a cancer type historically resistant to immunotherapy.
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Colorectal cancer is the second leading cause of cancer death in the United States. While overall death from CRC has declined, survival rates for advanced disease remain poor, with an increasing burden on younger populations. For the 95% of patients diagnosed with MSS mCRC, there are no approved immunotherapies, 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; 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.
Safety and Tolerability: There were no treatment related deaths in patients treated with the combination BOT/BAL, and side effects were manageable and consistent with immunotherapies.
Efficacy Results: In the 77 patients without active liver metastases with a median follow-up of 13 months, the Objective Response Rate (ORR) was 22% (17/77) and a majority of these responses were ongoing.
Long-term Benefits: Noteworthy are the durable responses observed in those without active liver metastases, with a median Duration of Response (DOR) not yet reached and the majority of patients (69%) alive at one year.
In a recent press release, Agenus disclosed updated results as of the data cutoff of March 1, 2024. 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.
Clinical Implications:
This research highlights the potential of BOT and BAL as a significant advancement in the immunotherapy landscape, particularly for MSS mCRC, the most common type of colorectal cancer which has no approved immunotherapies.
Future Directions:
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 U.S. Food and Drug Administration at a scheduled End-of-Phase 2 Meeting in July. A Phase 3 trial is planned to initiate later this year.
Access the Full Publication:
The full details of this study can be found here.
About Nature Medicine
Nature Medicine is a premier weekly scientific journal, publishing the finest peer-reviewed research across all fields of science and technology. Nature prides itself on providing cutting-edge studies that significantly advance knowledge and understanding in the scientific community. Only about 8% of the manuscripts submitted to Nature Medicine are accepted for publication, underscoring the journal’s stringent selection criteria and commitment to publishing only the most pioneering and 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. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.
Approximately 900 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.
About Colorectal Cancer
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, comprising an estimated 8.3% of cancer-related deaths annually. Although overall mortality from CRC has declined, survival remains poor for advanced disease, and the burden is shifting to a younger population. Alarmingly, from 1995 to 2019, the number of patients under the age of 55 who were diagnosed with CRC in the United States nearly doubled.