Triple combination therapy in colorectal cancer trial.

Array BioPharma and Pierre Fabre announced updated results from the 30 patient safety lead-in of the Phase III BEACON CRC trial evaluating the triplet combination of Erbitux + LGX 818 + MEK 162 (encorafenib + binimetinib + cetuximab) in patients with BRAF-mutant metastatic colorectal cancer (CRC) whose disease has progressed after one or two prior regimens. In patients with the BRAFV600E mutation, the estimated median progression-free survival (mPFS) at the time of analysis was 8 months. The confirmed overall response rate (ORR) in patients with the BRAFV600E mutation was 48%, and 3 patients achieved complete responses (CR). Further, the ORR was 62% in the 16 patients (10/16) who received only one prior line of therapy.

These data represent substantial improvements compared to several separate historical published standard of care benchmarks for this population. All patients with elevated baseline levels of the tumor markers CEA and CA19-9 had a reduction from baseline, with similar and substantial (median 83% - 96%) reductions across both markers in patients with objective responses and those with stable disease.

In the safety lead-in, the triplet combination was generally well-tolerated. Two patients discontinued treatment due to adverse events (AEs) with only one of these considered related to treatment. The most common grade 3 or 4 AEs seen in at least 10% of patients were fatigue (4/30), urinary tract infection (3/30), increased aspartate aminotransferase (AST; 3/30) and increased blood creatine kinase (CK; 3/30). The data were presented at the ASCO 2018 Gastrointestinal Cancers Symposium in San Francisco, California.

"Historical studies suggest that BRAF-mutant colorectal cancer patients who have progressed after first-line systemic treatment have an estimated median overall survival of less than 6 months," said Josep Tabernero, MD, PhD, Head of Medical Oncology and the Institute of Oncology at Vall d'Hebron University Hospital. The BEACON CRC trial will explore innovative combinations which have the potential to offer new treatment options to these patients who currently have few good choices remaining."