Agenus' New Immunotherapy Shows Promise Against Rising Colorectal Cancer in Americans Under 50

Agenus has announced promising results from a clinical trial assessing a new immunotherapy combination for microsatellite stable metastatic colorectal cancer (MSS mCRC), a form of cancer traditionally resistant to immunotherapy. The study's findings, published in Nature Medicine, demonstrate the potential effectiveness and safety of combining botensilimab (BOT), an enhanced anti-CTLA-4 antibody, with balstilimab (BAL), an anti-PD-1 antibody. This treatment strategy aims to stimulate the immune system to combat MSS mCRC, a condition that affects 95% of colorectal cancer patients and currently lacks approved immunotherapy options.

Colorectal cancer ranks as the second leading cause of cancer-related deaths in the United States, with a particularly poor prognosis for advanced stages. Although overall mortality rates have decreased, advanced cases continue to show poor survival outcomes, and the disease burden increasingly affects younger individuals.

In the Phase 1 trial, 148 heavily pre-treated MSS mCRC patients received the BOT/BAL combination. Of these, 101 had long-term follow-ups, and 77 did not have active liver metastases at the data cutoff on November 29, 2023. The study found no treatment-related deaths, with manageable side effects consistent with those typically observed in immunotherapy treatments.

Efficacy data revealed that, among the 77 patients without active liver metastases, the Objective Response Rate (ORR) was 22% after a median follow-up of 13 months. Most of these responses were ongoing, indicating durable benefits. Specifically, the median Duration of Response (DOR) had not yet been reached, and 69% of these patients were still alive after one year.

Updated results as of March 1, 2024, showed an increase in ORR to 23% among the same patient group, with a median follow-up of 13.6 months. The median DOR remained unreached, and the estimated 12-month and 18-month overall survival (OS) rates were 71% and 62%, respectively. The median OS was reported to be 21.2 months. The most common adverse effects included immune-related diarrhea or colitis, managed using standard therapies.

These findings suggest that the BOT/BAL combination could be a significant breakthrough in the treatment of MSS mCRC. The study's results underscore the potential of this novel immunotherapy to address a critical unmet need in cancer treatment.

Looking ahead, a randomized Phase 2 study has been completed to further evaluate the safety and efficacy of the BOT/BAL combination. Discussions with the U.S. Food and Drug Administration (FDA) are scheduled for an End-of-Phase 2 Meeting in July, with plans to initiate a Phase 3 trial later this year.

Botensilimab, designed to enhance both innate and adaptive anti-tumor immune responses, shows promise in treating "cold" tumors unresponsive to conventional therapies. Approximately 900 patients have participated in botensilimab trials, either alone or in combination with balstilimab, across various metastatic cancers.

Colorectal cancer remains a significant health challenge, accounting for 8.3% of cancer-related deaths annually in the U.S. Notably, the incidence of CRC in patients under 55 has nearly doubled from 1995 to 2019, highlighting an urgent need for effective treatments for younger populations.

Agenus, headquartered in Lexington, MA, is a leading immuno-oncology company focused on developing therapies for cancer and infectious diseases. The company's mission is to expand the benefits of cancer immunotherapy through innovative combination approaches. Their pipeline includes a broad spectrum of antibody therapeutics, adoptive cell therapies, and adjuvants.