OncoMatch/Clinical Trials/Crizotinib

Crizotinib (Xalkori) Clinical Trials

Crizotinib (Xalkori, PF-02341066) is an oral, first-in-class multi-targeted tyrosine kinase inhibitor of ALK, ROS1, and MET. It was the first ALK inhibitor approved for NSCLC — receiving accelerated FDA approval in August 2011 and regular approval in November 2013 for ALK-positive metastatic disease — and was later approved for ROS1-positive metastatic NSCLC in March 2016. In the Phase 3 PROFILE 1014 trial, first-line crizotinib improved progression-free survival and objective response rate (74% vs 45%) over platinum-pemetrexed chemotherapy in ALK-positive NSCLC, while the ROS1 cohort of the PROFILE 1001 trial showed an objective response rate of 66–72% (independent review to investigator-assessed, N=50) in ROS1-positive disease. Crizotinib also has documented activity against MET exon 14 skipping alterations and MET amplification, but it is not FDA-approved for MET-driven NSCLC, where capmatinib and tepotinib hold the biomarker-selected approvals. As a first-generation agent, crizotinib is now less commonly used as initial therapy where newer, more CNS-active inhibitors are available — alectinib, brigatinib, ensartinib, and lorlatinib for ALK, and entrectinib, repotrectinib, and taletrectinib for ROS1. It remains FDA-approved, and outside NSCLC was additionally approved in January 2021 for relapsed/refractory ALK-positive anaplastic large cell lymphoma (ALCL) in pediatric and young-adult patients, and in July 2022 for unresectable/recurrent/refractory ALK-positive inflammatory myofibroblastic tumor (IMT) in adult and pediatric patients. FDA-labeled NSCLC use is for patients with an ALK rearrangement or ROS1 fusion identified by an approved or validated test; individual trials set their own biomarker eligibility and accepted testing methods (NGS, FISH, or RT-PCR), and some additionally enroll MET exon 14-altered or MET-amplified disease.