Phase 2 study of combined therapy FOLFOX with dabrafenib and cetuximab/panitumumab as first-line treatment for patients with metastatic colorectal cancer MSS with BRAF V600E mutation.

TPS248 Background: The standard of first line therapy for patients with metastatic BRAF V600E- mutated and MSS phenotype metastatic inoperable colorectal cancer (mCRC), are combinations of oxaliplatin, fluoropyrimidines and bevacizumab or the FOLFOXIRI regimen with bevacizumab or combination encorafenib, anti-EGFR antibodies and FOLFOX. Taking into account availability of other BRAF inhibitors, the different spectrum of adverse events, differences in the price of various BRAF inhibitors, and the lack of access to encorafenib in many countries, we initiated a prospective study. We hypothesized that addition of dabrafenib and anti-EGFR antibodies to mFOLFOX6 regimen may represent an effective first-line therapy for patients with metastatic BRAF V600E- mutated MSS colorectal cancer. Methods: This phase 2 non-randomized, open-label, multicenter prospective study is designed to evaluate the efficacy and safety FOLFOX with dabrafenib and cetuximab or panitumumab in patients with previously untreated mCRC who have MSS and BRAF mutation in the first line of therapy in full doses after 8 courses in case of disease control dabrafenib and anti-EGFR therapy is continued as maintenance until disease progression or intolerable toxicity. Main inclusion criteria are: patients with histologically confirmed mCRC, who have MSS and BRAF mutation, adequate hematopoietic function and vital signs, and measurable disease according to RECIST v1.1. The primary endpoint is Objective Response Rate (ORR), secondary endpoints are Progression-free survival (PFS), time to objective response, duration of response (DOR), disease control rate, overall survival (OS), Incidence of adverse events (NCI CTCAE 5.0), Incidence of adverse events grade 3-4, frequency of dose reductions and drug withdrawals, biomarker studies to assess the causes of resistance. Statistical hypothesis: null hypothesis - objective response rate 40%, alternative hypothesis - objective response rate 60%. To accept the alternative hypothesis, with a first-order error of 0.05 and 90% power, 64 patients should be included. Enrollment began in January 2025 and is ongoing. Clinical trial information: NCT06978400 .