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ASCO GI 2023 | Botensilimab and balstilimab in metastatic, pre-treated MSS-CRC

Benjamin Schlechter, MD, Dana-Farber Cancer Institute, Boston, MA, presents expanded data from the microsatellite stable colorectal (MSS-CRC) expansion cohort of the Phase I study of botensilimab (NCT03860272), a multifunctional Fc-enhanced anti-CTLA-4, in combination with balstilimab, an anti-PD1 antibody, in metastatic heavily pre-treated MSS CRC. Efficacy was especially higher in patients without liver metastases, which form a significant minority of patients with MSS-CRC. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Gastrointestinal Cancers (GI) Symposium in San Francisco, CA.

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Transcript (edited for clarity)

So this is a second generation immune checkpoint inhibitor combination for refractory colorectal cancer. So we know that conventional checkpoint inhibitors don’t work in the most common forms of colorectal cancer, which is microsatellite stable disease. This is a modified version of a CTLA-4 inhibiting antibody that engages NK cells and does not fix complement. So it has supposedly a better safety profile...

So this is a second generation immune checkpoint inhibitor combination for refractory colorectal cancer. So we know that conventional checkpoint inhibitors don’t work in the most common forms of colorectal cancer, which is microsatellite stable disease. This is a modified version of a CTLA-4 inhibiting antibody that engages NK cells and does not fix complement. So it has supposedly a better safety profile. It likely has other mechanisms of actions that make it better than the prior generations of CTLA-4 inhibitors and why we’re seeing efficacy.

This is really the first checkpoint inhibitor combination to be efficacious in refractory colorectal cancer. A population of patients had prior 5FU, oxaliplatin and irinotecan who otherwise would be candidates for either Lonsurf or regorafenib, which are minimally effective drugs. The other interesting finding in this trial is that the efficacy seems to be confined to extra hepatic disease. And so while the majority of patients with colorectal cancer have liver mets, a significant minority, 20 to 30% don’t, and they benefit substantially. So I think the upcoming research questions are to continue to benefit those patients and then figure out how to get the patients with liver metastases to benefit from this new combination.

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