BEACON CRC: A randomized, 3-Arm, phase 3 study of Encorafenib (ENCO) and Cetuximab (CETUX)with or without Binimetinib (BINI) versus choice of either Irinotecan or FOLFIRI plus Cetuximab in BRAF V600E-mutant metastatic colorectal cancer.

Abstract

BRAF V600E mutations are identified in <=15% of metastatic colorectal cancer (mCRC) patients and confer a poor prognosis. In patient's refractory to initial therapy, ORR to standard chemotherapy and biologic combinations are generally <10%, with median PFS and OS of ~2 and 4-6 months, respectively. The BEACON CRC Study (NCT02928224) was a multicentre, randomized, open-label, 3-arm, phase 3 study evaluating ENCO + CETUX +/- BINI (triplet or doublet combination) versus investigator's choice of Irinotecan or FOLFIRI + CETUX (control) in patients with BRAF V600E-mutant mCRC who had failed one or two prior regimens in the metastatic setting. Primary endpoints were OS and ORR (blinded central review) for the triplet versus control arm; secondary endpoints included OS for the doublet versus control arm, as well as PFS, duration of response and safety. A total of 665 patients were randomly assigned to receive: triplet combination (n= 224), doublet combination (n= 220) or control regimen (n= 221). Median OS was 9.0 months (95% CI, 8.0-11.4) for the triplet versus 5.4 months (95% CI, 4.8-6.6) for control regimens (HR: 0.52; 95% CI, 0.39-0.70; P < .0001). ConfirmedORR(blinded central review) was 26% (95% CI, 18-35%) for the triplet versus 2% (95% CI, <1% to 7%) for control (P < .0001). Median OS for the doublet was 8.4months (95% CI, 7.5-11.0) (HR vs control, 0.60; 95% CI, 0.45-0.79; P = .0003). Adverse events (AEs) were consistent with prior trials with each combination. AEs >=grade 3 occurred in 58%, 50% and 61% of patients in the triplet, doublet and control arms, respectively. ENCO + BINI + CETUX improved OS and ORR in patients with BRAF V600E-mutant mCRC compared with current standard of care chemotherapy and had a safety profile consistent with the known safety profile of each agent. This targeted therapy regimen should be a new standard of care for this patient population.