MEK114653: A randomized, multicenter, phase II study to assess efficacy and safety of trametinib (T) compared with docetaxel (D) in KRAS-mutant advanced non-small cell lung cancer (NSCLC).

8029 Background: KRAS mutations are detected in 25% of NSCLC, and there are no approved targeted therapies for this subset of NSCLC. D, an approved second-line treatment for NSCLC, has a response rate of < 10%. T is a reversible, highly selective allosteric inhibitor of MEK1/2 activation and kinase activity. This phase II trial (NCT01362296) evaluated the efficacy of T vs D in pts with advanced KRAS-mutant NSCLC who had received prior platinum-based chemotherapy. Methods: Pts were randomized 2:1 to T (2 mg QD) or D (75 mg/m2 IV every 3 weeks) and stratified by type of mutational status and gender. Crossover to the other arm after progressive disease was allowed. Primary endpoint was PFS in pts with KRAS-mutant NSCLC (modified ITT; mITT). Secondary endpoints were OS, ORR, duration of response, and safety. PFS and OS were compared using a stratified log-rank test. The trial was stopped early for futility at a planned interim analysis; 92 PFS events were reported at the time of study termination. Results: Be...