Phase Ib Study of Crizotinib plus Pembrolizumab in Patients with Previously Untreated Advanced Non-Small Cell Lung Cancer with ALK Translocation

[摘要] Background. Previous research suggests single-agent crizotinib is efficacious for the treatment of anaplastic lymphoma kinase (ALK)–rearranged advanced non-small cell lung cancer (NSCLC). Methods. This study evaluated the safety and preliminary antitumor activity of crizotinib plus pembrolizumab as first-line therapy in patients with ALK-rearranged NSCLC. Patients were initially treated at dose level 0 (DL0) with crizotinib 250 mg twice daily and pembrolizumab 200 mg every 3 weeks (cycle duration was 3 weeks). If a dose-limiting toxicity occurred, subsequent patients were enrolled at a lower dose level (dose level −1 [DL −1]: 3 weeks of crizotinib monotherapy 250 mg twice daily, followed by crizotinib 250 mg twice daily with the addition of pembrolizumab 200 mg every 3 weeks). The primary endpoint was dose-limiting toxicity. Antitumor activity was assessed. Results. Nine patients were enrolled: two at DL0, then seven at DL−1. Dose-limiting toxicities occurred in four patients (grade 3 increases in alanine aminotransferase [ALT] and aspartate aminotransferase [AST] and grade 3 fatigue at DL0; grade 3 increase in ALT and grade 3 increases in both ALT and AST at DL−1). Conclusion. The maximum tolerated dose was not determined because slow accrual resulted in early study termination.

[学科分类] 地质学