Pharmacologic study ( JP 28927) of alectinib in Japanese patients with ALK+ 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 ( JP 28927). Eligible patients (≥20 years, locally advanced/metastatic ALK + disease, ALK inhibitor‐naïve and ‐pretreated [including crizotinib refractory]) were randomized 1:1 to receive one of two sequences of alectinib 300 mg 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 20/40 mg vs 150 mg; food effect with 150 mg; and safety. Thirty‐five patients were enrolled; median treatment duration was 13.1 months (range 1.1−15.0). Under fasting conditions, exposure of the two formulations was similar; mean AUC last  ± standard deviation 3230 ± 914 h·ng/ mL vs 3710 ± 1040 h·ng/ mL , respectively, for 150‐mg vs 20/40‐mg capsules. Food effect with 150 mg 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 1.2 months (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 13.9 months (95% CI 11.1−not reached) and 12.9 months (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.