Array BioPharma Inc. announced it has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for encorafenib (BRAFTOVI*), in combination with binimetinib (MEKTOVI*) and cetuximab for the treatment of patients with BRAFV600E -mutant metastatic colorectal cancer (mCRC) as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease.
BRAFv600 -mutant mCRC patients have a mortality risk more than double that of mCRC patients without the mutation, and currently there are no therapies specifically approved for this high unmet need population. [1-6]
Breakthrough Therapy Designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition where preliminary clinical evidence indicates that they may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
"We are delighted that the FDA has recognized the potential of this combination for patients with BRAF -mutant metastatic colorectal cancer," said Victor Sandor, M.D., Chief Medical Officer. "As there are no regimens approved specifically for BRAF -mutant mCRC, this designation provides us with the opportunity to work closely with the FDA to potentially accelerate our effort to bring an important treatment option to these patients in critical need."As presented at the ESMO 20 World Congress on Gastrointestinal Cancer in June 2018, the results from the safety lead-in of the ongoing randomized Phase 3 BEACON CRC trial showed that, at the time of analysis, the overall survival (OS) data were fully mature through 12.6 months and that the median OS had not yet been reached.
-One-year overall survival rate for this cohort was 62%.
-Median progression-free survival (mPFS) for patients treated with the triplet was 8 months [95% CI 5.6-9.3] and is similar between patients receiving one prior line of therapy and patients receiving two prior lines of therapy.
-Confirmed overall response rate (ORR) was 48% and among the 17 patients who received only one prior line of therapy the ORR was 62%.
-The triplet combination was generally welltolerated 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 blood creatine kinase (10%) and increased aspartate aminotransferase (10%).
The triplet combination of BRAFTOVI, MEKTOVI and cetuximab for the treatment of patients with BRAF -mutant metastatic colorectal cancer is investigational and not approved by the FDA.
 Kopetz et al., ASCO 2017
 De Roock et al., Lancet Oncol, 2010
 Ulivi et al., J Transl Med. 2012
 Peeters et al., ASCO 2014
 Saridaki et al., PLoS One. 2013
 Loupakis et al., Br J Cancer. 2009