Agenus Inc. (Nasdaq: AGEN), a pioneer in the development of immunological agents for cancer treatment, has recently unveiled promising results from an investigator-sponsored trial (IST) of its novel therapies, botensilimab and balstilimab (BOT/BAL), for treating colon cancer. These findings were presented at the 2024 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Munich, Germany, highlighting significant advances in neoadjuvant therapy for this difficult-to-treat cancer.

The study, led by Dr. Pashtoon Kasi, has shown remarkable results in the neoadjuvant setting, particularly for microsatellite stable (MSS) colorectal cancers—a group traditionally resistant to many forms of therapy. “The rapid and complete resolution of aggressive MSS colorectal cancer tumors observed in this study is unprecedented in the field,” remarked Dr. Kasi. He emphasized the transformative potential of the BOT/BAL combination therapy, noting, “The exceptional activity of this therapy in the neoadjuvant setting offers new hope for patients facing this challenging cancer subtype.”

The trial enrolled 20 patients, with pathology results available for all participants: 17 with MSS and 3 with high microsatellite instability (MSI-H). Treatment regimens varied between two cohorts: NEST-1 patients received an initial dose of both botensilimab and balstilimab, followed by a second dose of balstilimab two weeks later; NEST-2 patients received up to three additional doses of balstilimab.

The NEST-2 cohort demonstrated particularly striking outcomes, with 78% (7 out of 9) of MSS patients achieving pathologic responses of at least 50% tumor regression, and 56% (5 out of 9) experiencing complete pathologic responses. These results suggest a substantial potential to minimize the rate of disease recurrence and reduce the need for more invasive treatments and chemotherapy.

Dr. Steven O’Day, Chief Medical Officer at Agenus, highlighted the safety and efficacy of the treatment: “No surgeries were delayed due to adverse events, and no patients had unresolved immune-related adverse events.” He added that the side effects were manageable, and no new safety concerns emerged during the trial.

Botensilimab, a human Fc enhanced CTLA-4 blocking antibody, is designed to boost both innate and adaptive anti-tumor immune responses. Its innovative mechanism targets “cold” tumors, which typically do not respond well to conventional therapies. By priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells, and inducing long-term memory responses, botensilimab extends the benefits of immunotherapy to a broader range of tumor types.

With approximately 900 patients already treated in various clinical trials, botensilimab, alone or in combination with balstilimab, has shown clinical responses across nine metastatic, late-line cancers.

The significant advancements presented by Agenus at the ESMO Congress represent a potential paradigm shift in the treatment of MSS colon cancer. The promising results from this trial not only demonstrate the efficacy of the BOT/BAL combination in reducing tumor sizes but also pave the way for less invasive and more targeted therapeutic options for cancer patients.

The latest findings from Agenus Inc.’s trial are a testament to the ongoing innovations in cancer treatment, offering renewed hope and potentially life-extending options to patients with one of the most common and challenging cancers worldwide.

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