Array BioPharma announces interim results of Braftovi + Mektovi + Cetuximab for treatment of BRAFV600E-mutant metastatic colorectal cancer at the ESMO congress

Array BioPharma Inc. announced the presentation of results from the Phase III BEACON CRC trial evaluating the combination of Braftovi (encorafenib), a BRAF inhibitor, Mektovi (binimetinib), a MEK inhibitor, and Erbitux (cetuximab), an anti-EGFR antibody (Braftovi Triplet), in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two lines of therapy. Data presented included primary and secondary endpoints, waterfall plots describing tumor reduction, subgroup analyses, and exploratory analyses comparing overall survival (OS) of the Braftovi Triplet and Braftovi Doublet (Braftovi and cetuximab) in a subset of patients with mature follow-up, including the first 331 randomized patients, as well as safety and tolerability.

Results showed that BRAF-mutant mCRC patients treated with the Braftovi Triplet combination demonstrated a statistically significant improvement in OS (9.0 months vs. 5.4 months, [HR 0.52, (95% CI 0.39-0.70), p<0.0001]) and objective response rate (ORR) (26.1% vs. 1.9%, p<0.0001 as assessed by Blinded Independent Central Review (BICR)) compared to cetuximab plus irinotecan-containing regimens (Control). Median progression-free survival (mPFS) for patients treated with the Braftovi Triplet was 4.3 months [HR 0.38, (95% CI 0.29, 0.49), p<0.0001] compared to 1.5 months observed with the Control arm. These data were presented in an oral presentation on Saturday, July 6, at the ESMO 21st World Congress on Gastrointestinal Cancer in Barcelona , Spain.

The interim analysis also showed an improvement in secondary efficacy endpoints. Patients treated with the Braftovi Doublet demonstrated a statistically significant improvement in OS (median 8.4 months vs. 5.4 months, [HR 0.60, 95% CI (0.45-0.79), p=0.0003]) and ORR (20.4% vs. 1.9%, p<0.0001, per BICR) compared to Control. Further, mPFS for patients treated with the BRAFTOVI Doublet was 4.2 months [HR 0.40, 95% (CI 0.31-0.52), p<0.0001] versus 1.5 months with Control.

A descriptive comparison of the Braftovi Triplet to the Braftovi Doublet demonstrated a positive trend across endpoints including ORR and OS [HR 0.79, 95% CI (0.59-1.06)]. The control arm of the BEACON CRC trial was consistent with past reported studies and historical data across efficacy endpoints, underscoring that patients with BRAF-mutant mCRC generally have a poor prognosis with current available treatments. Currently there are no FDA -approved therapies specifically indicated for this high unmet need population. BRAF mutations are estimated to occur in up to 15% of patients with mCRC and V600E is the most common mutation.

The Braftovi Triplet and Doublet were generally well-tolerated with no unexpected toxicities. The safety profiles of the Braftovi Triplet and Doublet were consistent with prior reported experience with each regimen and with effects of MEK, RAF and EGFR therapies. Grade 3 or higher adverse events were seen in 58%, 50% and 61% of patients in the Braftovi Triplet, Doublet and Control arms respectively. Discontinuation of therapy due to adverse events was seen in 7%, 8% and 11% of patients in the Triplet, Doublet and Control arms respectively.

Comment:On May 21, 2019, Array announced initial results from the interim analysis of the Phase III BEACON mCRC trial, which showed statistically significant improvement in OS and ORR with the Braftovi Triplet compared to Control, reducing the risk of death by 48%.

Comment: Array intends to submit the results of the BEACON CRC trial for marketing approval in the second half of 2019.