ASCO 2026 | SWOG S2107: encorafenib, cetuximab, and nivolumab in BRAF V600E-m mCRC

SWOG S2107 is a randomized phase 2 trial that looks at comparing outcomes of patients with microsatellite stable BRAF V600E treatment of refractory metastatic colorectal cancer and is comparing encorafenib cetuximab based on the success of the previous Beacon study with the addition of anti-PD-1 therapy, encorafenib, cetuximab, and nivolumab. The reason that we were specifically interested in the combination of BRAF, EGFR, and PD-1 combination therapies was that we know that the MSS BRAF V600E population of patients with colorectal cancer are specifically enriched for kind of immune activation within their tumors. So we had done a preceding clinical trial at MD Anderson with encorafenib, cetuximab, and nivolumab in this population, 26 patients. We saw an overall response rate of 50%, median PFS of over seven months. And we saw multiple patients on that study who did well for several years. So we were seeing durable responses. The science and the correlative studies that came out of that went really well too. We saw that patients who had dynamic improvements and uptakes in their immune activation signatures, especially responded to the encorafenib, cetuximab, nivolumab in our trial at MD Anderson. Again, this was suggesting to us that the immunotherapy was working to boost the anti-tumor efficacy. So based on that rationale, we proceeded with the follow-up SWOG S2107 study. And this is the data that we’re reporting this week at ASCO. The median, or sorry, the primary endpoint for that study was progression-free survival. And among the 87 patients who were randomized, two to one to encorafenib, cetuximab, nivolumab, one-third of the patients got the control of encorafenib and cetuximab. We did not see an improvement in median progression-free survival with the addition of nivolumab to encorafenib and cetuximab. With the PD-1 targeted therapy combination, the median PFS was 6.3 months. With encorafenib cetuximab, it was 6.1 months. We also saw overall response rate of around 39% with encorafenib cetuximab and nivolumab, a response rate of 36% with encorafenib cetuximab. These results were a bit surprising to us because we looked at the Beacon study, overall response rate of 20%, median PFS of around four months. So the control arm in our study really outperformed the historical precedent based on the Beacon study. So the otherwise, you know, the combination of encorafenib, the cetuximab, and the nivolumab was safe and well-tolerated. The most common grade three events were fatigue and arthralgia. We did not have any grade five treatment-related deaths on study. And, you know, even though that the study was a negative study, I still think there’s going to be a lot to learn from this study. Based on our experience at MD Anderson, there are clearly some patients with MSS BRAF V600E who benefit from BRAF EGFR and PD-1 combination therapies. And I think that our future work moving forward will look at really digging in into deep correlative analyses to identify those patients who may especially benefit from the addition of immunotherapy moving forward so that we can hopefully one day personalize and refine further the treatment of MSS BRAF V600E colorectal cancer.

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