BEACON: A Randomised, Phase 3 Study of Encorafenib and Cetuximab +/- Binimetinib vs. Choice of Either Irinotecan or FOLFIRI plus Cetuximab in BRAF V600E–Mutant Metastatic Colorectal Cancer Patients
Session type: Clinical Trials Showcase
BRAF mutations are identified in up to 15% of metastatic CRC (mCRC) pts and confer poor prognosis. In pts who are refractory to initial therapy, objective response rates (ORR) to standard chemotherapy and biologic combinations are generally <10%, with median progression-free survival (PFS) and overall survival (OS) approximately 2 and 4–6 months (mo), respectively. A 30 pt safety lead-in (SLI) of the BEACON study assessed the safety, tolerability, and efficacy of the combination of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) in pts with BRAF V600E–mutant mCRC after failure of 1 or 2 prior regimens, demonstrated a confirmed ORR of 48% [95% CI: 29.4, 67.5], including complete responses (CR) in 3 pts, median PFS of 8.0 mo [95% CI: 5.9, 9.3], and mature median OS of 15.3 mo [95% CI: 9.6, NR]. The combination was generally well tolerated, confirming the dose selection of the triplet combination for the randomized portion of the study.
The BEACON Study (NCT02928224) is a multicenter, randomized, open-label, 3-arm, phase 3 study to evaluate ENCO+CETUX with/without BINI (vs. investigator’s choice of irinotecan or FOLFIRI + CETUX (control) in pts with BRAF V600E‒mutant mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. 665 pts were randomized. The primary endpoints are OS and ORR (blinded central review) comparing the triplet to the control arm; secondary endpoints include PFS, duration of response, time to response, and comparisons of the doublet to the triplet and control arms.
Results of the initial analysis, including efficacy and safety, will be reported.
In the SLI, the combination of ENCO+BINI+CETUX showed encouraging activity in pts with BRAF V600E‒mutant mCRC. This regimen may be a new standard of care if these results are confirmed in the randomized portion of the study.