Combination of Botensilimab and Balstilimab Shows Activity in Patients With Metastatic Microsatellite-Stable Colorectal Cancer

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A combination of the next-generation immunotherapies botensilimab and balstilimab showed clinical activity in treating patients with refractory metastatic microsatellite-stable (MSS) colorectal cancer, according to new findings presented by El-Khoueiry et al at the 2023 ASCO Gastrointestinal Cancers Symposium (Abstract LBA8).


MSS tumors account for the vast majority of colorectal cancers, and the first generation of immunotherapy drugs is known to have had little effect on them. While immunotherapy has succeeded in microsatellite-unstable colorectal cancers, only about 3% to 5% of advanced colorectal cancers are microsatellite unstable, and there are no approved immunotherapies for the far more common MSS colorectal cancers.

The novel antibody botensilimab is directed against the T-cell receptor cytotoxic T-lymphocyte–associated antigen 4, while the novel monoclonal antibody balstilimab is designed to block the checkpoint protein PD-1 from interacting with PD-L1 and PD-L2. By inhibiting this interaction, balstilimab is aimed at freeing the immune system to attack cancers.

Study Methods and Results

In the new phase Ia/Ib trial, researchers followed 70 patients with metastatic MSS colorectal cancer who had been previously treated with several lines of drugs—including immunotherapies—for a median of 7 months after receiving the combination therapy. During that period, 23% of the patients had a reduction in the size of their tumors, and the median duration of response was not reached. The researchers noted that the disease control rate was 76% (95% confidence interval [CI] = 60%–84%) and the 12-month overall survival rate was 63% (95% CI = 42%–75%). The patients who benefited most from the combination were those who did not have active metastatic cancer in their liver.

Treatment-related adverse events occurred in 91% of patients—including grade 3 adverse events in 40% of patients and grade 4 events in 3%. A total of 12% of patients discontinued both drugs as a result of adverse events.


“In patients with heavily pretreated metastatic [MSS] colorectal cancer, botensilimab plus balstilimab continues to demonstrate promising clinical activity with durable response, and was well tolerated, with no new immune-mediated safety signals,” the researchers emphasized.

“Harnessing the power of immune therapy in refractory colorectal cancer has been a key goal of multiple clinical trials in advanced colorectal cancer, but in [MSS] colorectal cancer, efforts have been universally disappointing,” explained lead study author Benjamin L. Schlechter, MD, Professor of Medicine at Harvard Medical School and a senior physician at the Gastrointestinal Cancer Treatment Center at Dana-Farber Cancer Institute. “These data are a meaningful and important advance in the care of this very sick population,” he concluded.

As a result of the findings, researchers are currently enrolling patients with MSS colorectal cancer in a randomized phase II trial to further examine the efficacy of botensilimab and balstilimab combination immunotherapy.

Disclosure: The research in this study was funded by Agenus. For full disclosures of the study authors, visit

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