Agenus Reports Phase-2 Meeting Results and Interim Data for BOT/BAL in MSS Colorectal Cancer

Agenus Inc. (NASDAQ: AGEN), based in Lexington, Massachusetts, recently announced significant developments from its end-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA). The meeting focused on the progress of its immunotherapy combination, botensilimab (BOT) and balstilimab (BAL), aimed at treating adult patients with relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC) without active liver metastases.

Key Takeaways from the EOP2 Meeting:

1. Dosing Regimen: The FDA agreed on the BOT/BAL combination dosing schedule. The proposed regimen includes 75mg of BOT administered every six weeks for up to four doses, in combination with 240mg of BAL every two weeks for up to two years.

2. Randomized Phase 2 Interim Data: Preliminary data from the Phase 2 trial suggest the best efficacy at the 75mg BOT/240mg BAL combination, showing an objective response rate (ORR) of 19.4% and a six-month survival rate of 90%. The data are continuously maturing.

3. Accelerated Approval: The FDA advised against using the current results to support an accelerated approval, citing concerns that the objective response rates might not correlate to a survival benefit.

4. Phase 3 Protocol Design: The FDA recommended, at Agenus’ discretion, including a BOT monotherapy arm in the Phase 3 study.

Dr. Steven O’Day, Agenus’ Chief Medical Officer, expressed high optimism driven by the enthusiasm of global clinical experts and promising clinical activity observed in both Phase 1 and Phase 2 studies. Agenus is committed to exploring all avenues to make BOT/BAL accessible to patients, including potential partnerships in the U.S. to ensure the success of the Phase 3 trial.

Previously disclosed Phase 1 trial data revealed an ORR of 23% in 77 MSS mCRC patients without active liver metastases, with a median follow-up of 13.6 months. The survival rates at six, twelve, and eighteen months were 86%, 71%, and 62%, respectively, with a median overall survival of 21.2 months. The interim Phase 2 data are consistent with these findings, showing an ORR of 19.4% and a six-month survival rate of 90% for the BOT 75mg/BAL combination. The safety profile remained manageable, with no new safety signals observed. Agenus plans to continue discussions with the FDA as more data become available and will present these findings at an upcoming medical conference.

The results are particularly significant given the limited advancements in MSS colorectal cancer treatments, which have left a substantial gap in effective therapies for patients. Michael Sapienza, CEO of the Colorectal Cancer Alliance, highlighted the urgent need for new treatment options due to the high incidence and mortality rates of MSS colorectal cancer and its rising diagnosis rates among younger individuals.

Agenus is also advancing its efforts to bring BOT/BAL to patients in Europe, with engagements planned with the European Regulatory Authority to explore registration paths. These discussions aim to align on the regulatory approval process for the BOT/BAL combination in Europe.

In addition to colorectal cancer, Agenus is exploring opportunities for BOT/BAL development in other tumor types where the combination has shown clinical activity, including lung, melanoma, and pancreatic cancers. The company anticipates presenting data from these programs at future medical conferences, such as the European Society for Medical Oncology (ESMO) in September 2024.

Botensilimab, a human Fc-enhanced CTLA-4 blocking antibody, is designed to enhance both innate and adaptive anti-tumor immune responses, extending immunotherapy benefits to "cold" tumors that typically respond poorly to standard treatments. Approximately 1100 patients have been treated with botensilimab in Phase 1 and Phase 2 clinical trials, showing clinical responses across nine metastatic, late-line cancers.

Colorectal cancer (CRC) remains a significant health challenge, being the second leading cause of cancer death in the United States. MSS colorectal cancer, which represents about 95% of CRC cases, has particularly poor survival outcomes, especially for advanced disease stages. The burden of CRC is increasingly affecting younger populations, with cases nearly doubling among those under 55 years old in the U.S. from 1995 to 2019.

Agenus, founded in 1994, is a leading immuno-oncology company focused on developing comprehensive immunological treatments for cancer. With a broad pipeline that includes antibody therapeutics, adoptive cell therapies, and adjuvants, Agenus continues to leverage its end-to-end development capabilities to combat cancer effectively.

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