Botensilimab/Balstilimab Boosts Survival in Non-MSI-H Metastatic CRC

The combination of botensilimab and balstilimab demonstrated significant survival benefits in patients with non-MSI-H metastatic colorectal cancer.

A new treatment combination may improve survival rates for patients with non-microsatellite instability-high (non-MSI-H) metastatic colorectal cancer, according to data released from the immuno-therapy company Agenus at a late-breaking session at the 2023 European Society for Medical Oncology World Congress on Gastrointestinal Cancer (ESMO GI) on June 30.

The combination of botensilimab (a humanized antibody) and balstilimab (an immune checkpoint inhibitor) demonstrated significant survival benefits. After the botensilimab and balstilimab combination was granted a Fast Track Designation by the FDA earlier this year, it has been shown as an effective treatment combination for non-MSI-H metastatic colorectal cancer, compared with previous resistance to chemotherapy and immunotherapy, according to Agenus.

Within the study from Agenus, 101 patients with refractory (disease that does not respond to treatment) non-MSI-H metastatic colorectal cancer were eligible participants and received botensilimab every six weeks and balstilimab every two weeks. This pool of patients had a median of four previous lines of therapy and 25% of the patients had failed previous immunotherapy, according to the study. Eighty-seven of the 101 total patients underwent a six-week post-baseline imaging scan, in which 69 of these patients did not have active liver metastases.

"The new survival data underscore the potential of the botensilimab/balstilimab combination as an important treatment option for patients with non-MSI-H colorectal cancer,” said Dr. Andrea Bullock, study investigator and assistant professor of medicine at Harvard Medical School. “The patients in our study face one of the most challenging cancers to treat and represent the largest patient population with colorectal cancer where only a quarter of patients survive beyond one year with standard of care therapy. Botensilimab plus balstilimab continues to show deep and durable responses with 69% of objective responses still ongoing at the data cutoff."

According to the results from the study, there was an estimated rate of 74% for 12-month overall survival (OS, the period from diagnosis or treatment where patients are still alive) for patients without active liver metastases. The study also established that the median OS was 20.9 months for patients without active liver metastases. For patients with active liver metastases, the study determined that there was an estimate of 30% for OS and a median OS of 8.7 months.

Standard of care benchmarks (which determine sufficiency of professional obligations to patients from organizations) for patients with and without active liver metastases were 5.9 and 12.9 months, respectively, both surpassing the previous benchmarks of standard of care.

Regardless of the RECIST 1.1 responses (criteria defining the status of a tumor), the use of both botensilimab and balstilimab showed signs of better survival outcomes, according to Agenus. The study determined that no new safety concerns emerged when using the combination of botensilimab and balstilimab.

"The data from our expanded cohort demonstrate remarkable median overall survival and sustained responses in heavily pre-treated patients that historically haven’t responded to immunotherapy,” said Dr. Steven O’Day, chief medical officer at Agenus. “These findings provide evidence of the benefit of botensilimab/balstilimab in metastatic colorectal cancer, the second leading cause of cancer death in the U.S."

Agenus plans on submitting a Biologics License Application to the Food and Drug Administration (FDA) for patients with non-MSI-H metastatic colorectal cancer after seeing positive results from the trial. As for developments underway, Agenus plans to begin global randomized phase 2 trials for the botensilimab and balstilimab combination for melanoma and botensilimab with chemotherapy for patients with pancreatic cancer. The organization also plans to begin phase 3 studies regarding colorectal and non-small cell lung cancer (NSCLC).

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