Phase 1/2 study of ceritinib in Chinese patients with advanced anaplastic lymphoma kinase-rearranged non–small cell lung cancer previously treated with crizotinib: Results from ASCEND-6

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Background Patients with anaplastic lymphoma kinase-rearranged ( ALK +) non–small cell lung cancer (NSCLC) treated with crizotinib inevitably relapse, with brain as common site of progression. Patients and methods ASCEND-6, a phase 1/2, single-arm study, included adult Chinese patients with stage IIIB or IV ALK + NSCLC pretreated with crizotinib as the last therapy (irrespective of prior chemotherapies [≤2]). Primary endpoints were pharmacokinetics (PK), safety, and tolerability. Key secondary endpoint was overall response rate (ORR; investigator assessed). Results Of the 103 enrolled patients, all received prior crizotinib, 70 % received ≥1 prior chemotherapy regimen, and 63.1 % had brain metastases at baseline. In the phase 1 component, 20 patients completed a 5-day PK run-in period. Median T max (n = 16) was ∼6 h; geometric means of AUC 0–24 h (n = 16) and C max (n = 16) at steady state were 22,000 ng*h/mL and 1080 ng/mL, respectively. In the final analysis, median follow-up time was 34 months (range: 27.8–40.6). The ORR was 41.7 % (95 % confidence interval [CI]: 32.1–51.9), and median progression-free survival was 7.2 months (95 % CI: 4.1–7.5). Median overall survival was 17.5 months (95 % CI: 10.8–24.3). Most frequent adverse events, regardless of study drug relationship (mostly grade 1/2), were diarrhea (74.8 %), vomiting (62.1 %), alanine transaminase increased (59.2 %), aspartate transaminase increased (58.3 %), and nausea (58.3 %). Conclusions Ceritinib PK in Chinese patients is consistent with those observed in the global ASCEND-1 study. Ceritinib was well tolerated and showed durable responses in Chinese patients with ALK + NSCLC who progressed after crizotinib and ≤2 prior lines of chemotherapy.