Pharmacologic study (JP28927) of alectinib in Japanese patients with ALK plus non-small-cell lung cancer with or without prior crizotinib therapy

We report pharmacokinetics, efficacy and safety data for a new 150-mg alectinib capsule in ALK+ non-small-cell lung cancer in a multicenter, open-label pharmacologic study (JP28927). Eligible patients (20years, locally advanced/metastatic ALK+ disease, ALK inhibitor-naive and -pretreated [including crizotinib refractory]) were randomized 1:1 to receive one of two sequences of alectinib 300mg twice daily (comprising different schedules of 20/40-mg and 150-mg capsules) until investigator-determined lack of clinical benefit. Co-primary endpoints were: bioequivalence of alectinib 20/40mg vs 150mg; food effect with 150mg; and safety. Thirty-five patients were enrolled; median treatment duration was 13.1months (range 1.1-15.0). Under fasting conditions, exposure of the two formulations was similar; mean AUC(last)+/- standard deviation 3230 +/- 914h<bold>ng</bold>/mL vs 3710 +/- 1040h<bold>ng</bold>/mL, respectively, for 150-mg vs 20/40-mg capsules. Food effect with 150mg alectinib was negligible. Treatment-related adverse events in >20% of patients were constipation (31.4%), dysgeusia (25.7%), and decreased white blood cell and neutrophil count (22.9% each). No treatment-related grade 4/5 events occurred. Median time to response was 1.2months (95% CI 1.1-2.1). For the full analysis set (n=35) and crizotinib-failure subpopulations (n=23), the overall response rate was 70.0% (95% CI 50.6-85.3) and 65.0% (95% CI 40.8-84.6), and median progression-free survival was 13.9months (95% CI 11.1-not reached) and 12.9months (95% CI 3.9-not reached), respectively. The 150-mg capsule had a similar exposure profile to 20/40-mg capsules. Alectinib demonstrated promising efficacy and was well tolerated.