Cotellic

Cotellic (cobimetinib) is indicated for previously untreated, BRAF V600 mutation-positive unresectable or metastatic melanoma. Efficacy was evaluated in a single, adequate and well-controlled, multicenter, international, randomized (1:1), open-label trial. The trial demonstrated a PFS Hazard Ratio of 0.56 (95% CI: 0.45, 0.70; p-value: < 0.001), with a median PFS of 12.3 months compared to 7.2 months in the comparator arm. The OS Hazard Ratio was 0.63 (95% CI: 0.47, 0.85; p-value: 0.0019), with a median OS of NR months compared to 17.0 months in the comparator arm. The Overall Response Rate (ORR) was 70% compared to 50% in the comparator arm.

Notable safety findings include 26% of patients experiencing serous retinopathy in the cobimetinib plus vemurafenib arm. Grade 3 or 4 laboratory abnormalities included AST (9%) and creatine phosphokinase (13%). 15% of patients discontinued cobimetinib due to adverse reactions. The half-life of cobimetinib is 44 hours. Strong CYP3A inhibitors can increase cobimetinib exposure by 6.7-fold, while strong CYP3A inducers can reduce exposure by more than 80%.

Cotellic received Orphan Drug Designation on January 31, 2014. The IND was allowed to proceed on September 30, 2010. The application number is 206192Orig1s000.