The Phase I/II study sponsored by BMS/Pfizer in collaboration with NCI evaluating the triplet combination of encorafenib + cetuximab + nivolumab in MSS mCRC patients who have received prior treatment with at least one, but not more than two systemic chemotherapy regimen for mCRC
In September 2021, USFDA approved Braftovi (encorafenib) and Erbitux (cetuximab) combination to treat BRAF V600E mutated adult patients after prior therapy for mCRC based on the results from the BEACON Colorectal Cancer trial. The approval of the combination was not indicated in patients who were MSS, but the ongoing study is evaluating BRAF V600E who have MSS status.
With a data cutoff of February 2022, all patients are enrolled: 26 evaluable for toxicity and 23 for the response. The median age was 60 years (range, 32-85), and 16 (62%) were female. Grade 3+ treatment-related adverse events (AE)occurred in 15% patients. The overall response rate was 50%, and the disease control rate was 96%. Median PFS is 7.4 months. For the 11 patients with responses, the median duration of response is 7.4 months. Median OS is 15.1 months. The median follow-up was 11.4 months; the median duration of response was 7.4 months. E-slices showed concordance between patients with radiographic responses and reduction in cell viability and between non-responders and increase in cell viability.
“Encorafenib, cetuximab, and nivolumab appear to be a safe and well-tolerated combination for microsatellite-stable BRAF-mutated metastatic colorectal cancer. The efficacy of this combination appears promising when considering the precedent of encorafenib and cetuximab alone from the previously reported BEACON study.”–Expert Opinion.
The triplet combination immunotherapy approach targets a subset of patients with Microsatellite-stable mCRC patients, for which immunotherapy alone has proven to be historically ineffective. Also, these patients often experienced rapid progression, and their disease has shown not to be responsive to standard chemotherapy as other mCRC patients do. Putting in to context, the findings from the Phase III BEACON trial, which led to the approval of encorafenib + cetuximab for previously treated BRAF V600E- mutated mCRC, the doublet combination was found to be effective only in 20% of patients with a median progression-free survival (mPFS) of 4 months and median overall survival (mOS) of 9.3 months. The results of the triplet combination are more significant if we compare it with the doublet combination. Additionally, another phase II (SWOG 2017) trial is underway to evaluate the encorafenib and cetuximab with or without nivolumab in the same patient segment.