Tuesday January 15, 2019 0 comments
BOULDER -- Array BioPharma Inc. (Nasdaq: ARRY) today announced updated safety and efficacy results, including mature overall survival (OS), from the safety lead-in of the Phase 3 BEACON CRC trial evaluating the triplet combination of BRAFTOVI® (encorafenib), a BRAF inhibitor, MEKTOVI® (binimetinib), a MEK inhibitor and ERBITUX® (cetuximab), an anti-EGFR antibody, in patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC).
Array said the results showed that mature median OS was 15.3 months (95% CI, 9.6–not reached) for patients treated with the triplet. These data will be presented on Jan. 19 at the ASCO 2019 Gastrointestinal Cancers Symposium in San Francisco.
Updated median progression-free survival (mPFS) and updated confirmed overall response rate (ORR) results for patients treated with the triplet in the safety lead-in remain the same, as previously reported, with 8 months mPFS (95% CI, 5.6-9.3) and a 48% ORR (95% CI, 29.4–67.5). Among the 17 patients who received only one prior line of therapy, the ORR was 62%.
A BRAF mutation is present in up to 15% of all patients with mCRC and V600 is the most common BRAF mutation. [1-5] BRAFV600E-mutant mCRC patients have a mortality risk more than double that of mCRC patients without the mutation, and currently there are no U.S. Food and Drug Administration (FDA)-approved therapies specifically indicated for this high unmet need population. [3-10]
"The mature median overall survival of 15.3 months demonstrated in the safety lead-in of the BEACON CRC trial is unprecedented in this patient population and, for context, represents a substantial improvement compared to the observed historical published benchmarks of approximately 4 to 6 months for median overall survival with current standards of care in patients with BRAF-mutant mCRC," said Axel Grothey, BEACON CRC trial lead investigator and co-chair of the National Cancer Institute's Gastrointestinal Cancer Steering Committee, West Cancer Center, Memphis, TN.
"These updated data further underscore the potential of this triplet for patients with BRAF-mutant mCRC who are in desperate need of effective new treatment options."
Array said the triplet combination was generally well-tolerated with no unexpected toxicities. The most common grade 3 or 4 adverse events seen in at least 10% of patients were fatigue (13%), anemia (10%), increased creatine phosphokinase (10%), increased aspartate aminotransferase (10%) and urinary tract infections (10%). The rate of grade 3 or 4 skin toxicities continued to be lower than generally observed with ERBITUX in mCRC, the company said.
"We are delighted with the updated results from the BEACON CRC safety lead-in,” said Victor Sandor, Array’s chief medical officer.
“Following consultations with the FDA and European Medicines Agency, we initiated an amendment to the BEACON CRC protocol to allow for an interim analysis based primarily on confirmed ORR and durability of response endpoints, which we believe could support an accelerated approval with positive results.
"We anticipate topline results from this interim analysis in the first half of this year. This timing allows for the subset of patients required for the interim analysis of ORR to achieve a response and for the durability of responses to be appropriately evaluated."
On Aug. 7, 2018, Array announced 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.