BEACON CRC: safety lead-in (SLI) for the combination of binimetinib (BINI), encorafenib (ENCO), and cetuximab (CTX) in patients (pts) with BRAF-V600E metastatic colorectal cancer (mCRC)

Abstract

Background: Phase 2 data for the combination of ENCO (a selective BRAF inhibitor) +CTX (an anti‐EGFR antibody) in pts with BRAFV600E mCRC showed the regimen was well tolerated and improved response rate, progression‐free survival, and overall survival compared with historical controls. BEACON CRC (NCT02928224) is a randomized phase 3 study evaluating both the triplet combination BINI (a MEK inhibitor) +ENCO +CTX and the doublet combination ENCO + CTX compared with investigators' choice of irinotecan (IRI)+ CTX or FOLFIRI (folinic acid, 5‐fluorouracil, and IRI) +CTX in pts with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. Here we describe the results of the SLI to determine the safety of the triplet combination. Methods: Nine pts with BRAFV600E mCRC would receive ENCO 300 mg QD+ BINI 45 mg BID + CTX 400 mg/m2 (then 250 mg/m2 QW) in 28‐day cycles. If<33% of pts had a dose‐limiting toxicity (DLT), 16‐21 additional pts would be treated at the same dose. If≥33% of pts had a DLT, lower doses of BINI and/or ENCO would be assessed. Results: Thirty pts received the initial dose level; median age was 59 years, 17 pts were female, and 17 had an ECOG PS of 0. DLTs were reported in 5 pts: infusion reaction following CTX (n=2), inability to receive ≥75% dose intensity due to grade 2 retinopathy (n=2), and grade 2 decreased ejection fraction (n=1). The most common adverse events (% of pts with grade 1, 2, 3, 4) were diarrhea (38, 28, 3, 0), nausea (41, 3, 0, 0), dermatitis acneiform (38, 7, 0, 0), and fatigue (21, 14, 7, 0). Twenty‐eight pts continue on treatment; 1 pt died due to rapid disease progression and 1 pt discontinued due to disease‐related biliary obstruction. Preliminary efficacy data support the benefit of adding BINI to the doublet regimen; additional follow‐up will provide mature safety and efficacy data from the SLI cohort and will be presented. Conclusions: ENCO +BINI + CTX, at the full planned dose of each agent, was generally well tolerated. Safety and preliminary efficacy data support the initiation of the phase 3 portion of the BEACON trial.