Major Tumor Reductions in Neoadjuvant MSS Colon Cancer Patients Treated with Botensilimab/Balstilimab at ESMO GI Conference

Agenus Inc. (Nasdaq: AGEN), a prominent player in the development of innovative immunotherapy treatments for cancer, has announced significant findings from an investigator-sponsored trial (IST) assessing the combination of botensilimab and balstilimab (BOT/BAL) in a neoadjuvant setting for colon cancer. These findings were presented at the 2024 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Munich, Germany.

Dr. Pashtoon Kasi, the primary investigator of this landmark study, remarked on the groundbreaking results: “The rapid and complete resolution of aggressive MSS colorectal cancer tumors observed in this study is unprecedented in the field. The exceptional activity of the BOT/BAL combination therapy in the neoadjuvant setting offers new hope for patients facing this challenging cancer subtype. Furthermore, the pattern of response and the lack of clinical recurrence speaks to the curative potential of one’s own body to fight cancer.”

Key highlights from the study are as follows:

Enrollment and Treatment Regimens:
The trial enrolled 20 patients who were evaluable with available pathology results, comprising 17 patients with microsatellite stable (MSS) colon cancer and 3 with high microsatellite instability (MSI-H). Both cohorts received an initial dose of botensilimab with balstilimab. While the NEST-1 cohort received an additional dose of balstilimab two weeks later, the NEST-2 cohort received up to three additional doses of balstilimab.

Clinical Findings:
The results demonstrated remarkable tumor regression, particularly among the MSS patients in the NEST-2 cohort. Specifically, 78% (7 out of 9) of MSS patients in this cohort achieved pathologic responses of at least 50% tumor regression, with 56% (5 out of 9) reaching complete pathologic responses. Surgical outcomes were favorable, with no delays due to adverse events and no unresolved immune-related adverse events. Side effects were manageable, and no new safety concerns were identified.

Pathologic Response Data:
- In the NEST-1 cohort (N=10), 63% (5 out of 8) of MSS patients and 100% (2 out of 2) of MSI-H patients achieved over 50% tumor regression. Complete pathologic responses were observed in 13% (1 out of 8) of MSS patients and 50% (1 out of 2) of MSI-H patients.
- In the NEST-2 cohort (N=10), 78% (7 out of 9) of MSS and 100% (1 out of 1) of MSI-H patients achieved over 50% tumor regression. Complete pathologic responses in this cohort were 56% (5 out of 9) for MSS and 100% (1 out of 1) for MSI-H patients.
- Overall, 71% (12 out of 17) of MSS and 100% (3 out of 3) of MSI-H patients achieved over 50% tumor regression. Complete responses were seen in 35% (6 out of 17) of MSS and 67% (2 out of 3) of MSI-H patients.

Dr. Steven O’Day, Chief Medical Officer at Agenus, highlighted the transformative potential of this therapy: “The significant tumor reductions observed with the early use of BOT/BAL therapy before surgery underscore its paradigm-changing potential in neoadjuvant colon cancer, potentially minimizing the rate of disease recurrence and the need for invasive procedures and chemotherapy in the future. The responses in MSS patients were particularly profound, and extending the treatment duration in the NEST-2 cohort further amplified these effects. We are focused on expanding BOT/BAL’s application in the neoadjuvant setting to improve treatment for individuals living with cancer.”

About Botensilimab:
Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to enhance both innate and adaptive anti-tumor immune responses. Its unique design targets "cold" tumors, which typically respond poorly to conventional therapies. Botensilimab has shown efficacy across various tumor types by activating T cells, reducing regulatory T cells within tumors, and stimulating myeloid cells to induce long-term memory responses. Approximately 900 patients have been treated with botensilimab in phase 1 and phase 2 trials, either alone or in combination with balstilimab.

About Colorectal Cancer:
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States, accounting for approximately 8.3% of annual cancer deaths. Despite a decline in overall CRC mortality, survival rates for advanced disease remain poor, with a troubling increase in cases among younger individuals.

About Agenus:
Agenus is a leading immuno-oncology company focused on developing treatments for cancer and infectious diseases. The company leverages a vast portfolio of antibody therapeutics, adoptive cell therapies, and adjuvants to enhance cancer immunotherapy's reach and efficacy.

The remarkable findings from this study suggest the potential for BOT/BAL therapy to revolutionize the treatment paradigm for colon cancer, offering new hope and improved outcomes for patients with this challenging disease.

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