Open AccessPhase Ib Study of Crizotinib plus Pembrolizumab in Patients with Previously Untreated Advanced Non‐Small Cell Lung Cancer with ALK Translocation
Author(s) -
Patel Sandip Pravin,
Pakkala Suchita,
Pennell Nathan A.,
Reckamp Karen L.,
Lanzalone Silvana,
Polli Anna,
Tarazi Jamal,
RobertVizcarrondo Francisco
Publication year - 2020
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2020-0034
Subject(s) - crizotinib , medicine , anaplastic lymphoma kinase , lung cancer , pembrolizumab , alk inhibitor , ceritinib , oncology , alectinib , toxicity , gastroenterology , cancer , immunotherapy , malignant pleural effusion
Lessons Learned This study evaluating first‐line crizotinib plus pembrolizumab in patients with anaplastic lymphoma kinase (ALK)–positive advanced non‐small cell lung cancer (NSCLC) was terminated early because increased availability of second‐generation ALK inhibitors resulted in difficulty identifying and accruing eligible patients. In the small number of patients enrolled, elevated transaminases were the most common treatment‐related toxicity. No other relevant toxicities were observed. Although no definitive conclusions could be drawn because of the small number of patients studied, the higher frequency of severe transaminase increases noted in this sample should be of concern if ALK inhibitor and PD‐L1/PD‐1 inhibitor combinations are tested in future studies.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.