Array BioPharma, based in Boulder, Colorado, announced positive results from its Phase III BEACON CRC trial. The trial evaluated a triple combination of Braftovi (encorafenib), a BRAF inhibitor, Mektovia (binimetinib), a MEK inhibitor, and Erbitux (cetuximab), an anti-EGFR antibody, in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC) after one or two lines of therapy. The triple-combination almost doubled overall survival in the patient subpopulation.
The patients who received the therapy, dubbed Braftovi Triplet, showed a statistically significant improvement in overall survival (OS) and objective response rate (ORR) compared to cetuximab plus irinotecan-containing regimens. Median progression-free survival (mPFS) for patients receiving Braftovi Triplet was 4.3 months compared to 1.5 months.
Array presented the data on July 6 at the ESMO 21st World Congress on Gastrointestinal Cancer in Barcelona, Spain.
“It’s exciting to see the interim analysis results from the potentially practice-changing BEACON CRC trial, which demonstrated a significant improvement in outcomes compared to available standard of care options for patients with BRAFV600E-mutant metastatic colorectal cancer,” stated Scott Kopetz, Associate Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.
Kopetz added, “These data add to the body of evidence supporting the Braftovi Triplet as a potential new standard of care regimen for this patient population, who currently have limited treatment options available.”
Colorectal cancer is the third most common type of cancer in men and second most common in women. In the U.S., about 140,250 people were diagnosed with cancer of the colon or rectum in 2018, and worldwide, there were about 18 million new diagnoses last year. About 50,000 people die of the disease each year.
The specific BRAF mutations appear in about 15% of mCRC patients, and typically represent a poor prognosis. The V600 mutation is the most common BRAF mutation, causing risk of mortality more than two times higher than those with the so-called normal or wildtype BRAF.
Kopetz tweeted the response rates in second-line patients was 34% with the triplet compared to 22% for doublet and 2% for standard-of-care chemotherapy.
“Colorectal cancer does not respond to BRAF therapy alone because tumor cells adapt through other mechanisms after initial treatment,” Kopetz stated. “With this triple targeted therapy, we are using a very scientifically logical combination to inhibit BRAF and these other mechanisms.”
Pierre Fabre licensed the rights to Braftovi and Mektovi to Array in 2015 for $30 million upfront and up to $425 million in milestones. Erbitux is marketed by Eli Lilly.
The two Array drugs face competition from Novartis and Roche. Also, Novartis’ MEK-BRAF inhibitor two-drug combination, Mekinist (trametinib) and Tafinlar (dabrafenib), is the primary competitor. That combo grew 31% to $1.12 billion in sales in 2018.
Pfizer bought Array in June for about $11.4 billion. The deal is expected to close later this year. Pfizer indicated at the time that the two drugs, Braftovi and Mektovi, “have significant potential for long-term growth via expansion into additional areas of unmet need and is currently being investigated in over 30 clinical trials across several solid tumor indications, including the Phase III BEACON trial in BRAF-mutant metastatic colorectal cancer (mCRC).”