Array BioPharma announced positive results from the interim analysis of the Phase 3 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 BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two prior lines of therapy. The trial met both primary endpoints of confirmed objective response rate (ORR), as assessed by Blinded Independent Central Review (BICR), and overall survival (OS). Array intends to submit these results of the BEACON CRC trial for marketing approval in the second half of 2019.

Results from the trial showed that BRAF-mutant mCRC patients treated with the BRAFTOVI Triplet demonstrated a statistically significant improvement in ORR (26.1% vs. 1.9%, p<0.0001, per BICR) and OS (median 9.0 months vs. 5.4 months, [HR 0.52, 95% CI (0.39-0.70), p<0.0001]) compared to cetuximab plus irinotecan-containing regimens (Control).

"The BEACON CRC trial is the first Phase 3 trial in patients with BRAFV600E-mutant mCRC and these results show a significant improvement compared to available standard of care options for this patient population," said Scott Kopetz, M.D., Ph.D., FACP, Associate Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. "Given that there are no therapies currently FDA-approved for this patient population, I believe the results of the BEACON CRC trial will be practice-changing."

The analysis of ORR was based on the first 331 randomized patients, while the interim analysis of OS included all 665 randomized patients, and was based on a data cutoff date in February of 2019, approximately two weeks after the last patient was enrolled. Future analyses will assess ORR on the total population and OS with longer follow up.

Results from the secondary endpoint analysis showed that patients treated with the combination of BRAFTOVI and cetuximab (BRAFTOVI Doublet) demonstrated a statistically significant improvement in ORR (20.4% vs. 1.9%, p<0.0001, per BICR) and OS (median 8.4 months vs. 5.4 months, [HR 0.60, 95% CI (0.45-0.79), p=0.0003]) compared to 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), nominal p=0.1164].

In patients receiving one prior line of therapy, ORR as assessed by BICR was 34.3% with the BRAFTOVI Triplet and 22.4% with the BRAFTOVI Doublet, while at this time the OS for both arms is consistent with that seen in the overall population.

"We are pleased to announce positive results from the BEACON CRC trial, including that the BRAFTOVI Triplet reduced the risk of death by 48% versus control," said Ron Squarer, CEO, Array BioPharma. "We are deeply grateful to the patients and investigators whose participation has helped bring us one step closer to delivering a new standard of care for patients with BRAF-mutant mCRC. This has the potential to be the first chemotherapy-free, targeted regimen for mCRC patients, a population with a very high unmet need for effective treatments."

As demonstrated in the control arm of the BEACON CRC trial and consistent with historical data, patients with BRAF-mutant mCRC generally have a poor prognosis with currently available treatments and 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.

In March 2019, the National Comprehensive Cancer Network® (NCCN®) updated their Clinical Practice Guidelines in Oncology for Colon and Rectal Cancer to include BRAFTOVI in combination with MEKTOVI and an anti-EGFR antibody as a Category 2A treatment for patients with BRAFV600E-mutant mCRC, after failure of one or two prior lines of therapy for metastatic disease. The NCCN based their recommendation on data from the safety lead-in of the BEACON CRC trial.

On August 7, 2018, Array announced that the FDA granted Breakthrough Therapy Designation to BRAFTOVI, in combination with MEKTOVI and ERBITUX for the treatment of patients with BRAFV600E-mutant mCRC as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease.

The triplet combination of BRAFTOVI, MEKTOVI and ERBITUX for the treatment of patients with BRAFV600E-mutant mCRC is investigational and not approved by the FDA.

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