ASCO GI 2022 | A Phase I/II investigating the addition of IO to the standard of care for patients with MSS mCRC

Van K. Morris, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, outlines the Phase I/II trial evaluating the addition of the immune checkpoint inhibitor, nivolumab, to the standard of care (SOC), encorafenib plus cetuximab, for patients with stage 4 microsatellite stable (MSS), BRAFV600E metastatic colorectal cancer (mCRC), who often suffer from poor overall survival (OS) rates, and who have had 1 or 2 lines of prior therapy excluding targeted BRAF and immunotherapies. This is the first time the SOC plus an immunotherapy has been in investigated in this patient population. In the first stage of this Phase I/II study, safety was explored to ensure a favorable safety profile in 15 patients, where if three or more responses were observed, an additional 11 patients would be recruited. As of January 2022, 26 patients were recruited onto the trial, 22 of which have shown a response to the novel combination, with the combination appearing safe and well tolerated. No patients exhibited any dose-limiting toxicities in the initial cohort and no treatment-related deaths have been observed thus far. 3 or 4 treatment-related adverse events occurred in fewer than 20% of patients. Radiographic responses have been demonstrated in 11 of the 22 patients, with an overall response rate (ORR) of 50% and a disease control rate of 96%. Dr. Morris acknowledges the limitation of the study as a single institute and single arm trial and so to fully and reliably address the question of whether the addition of immunotherapy has an improved benefit to this patient population, a randomized trial will be performed in the coming months across the US assessing treatment of encorafenib plus cetuximab with or without nivolumab. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2022.