Data from Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non–Small Cell Lung Cancer—Results from the Drug Rediscovery Protocol

<div>AbstractPurpose:<p> To provide patients with <i>MET</i>-mutated advanced non–small cell lung cancer (<i>MET</i>mut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.</p>Patients and Methods:<p>In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring <i>MET</i> exon 14 skipping or other <i>MET </i>mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity. Primary endpoints were clinical benefit [CB: RECIST v1.1 confirmed partial response, complete response (CR), or stable disease ≥16 weeks] and safety. Patients were enrolled using a Simon-like two-stage design, with eight patients in stage I and if ≥1/8 patients had CB, 24 patients in stage II. Whole-genome sequencing and RNA sequencing were performed on baseline biopsies.</p>Results:<p>Between September 2018 and October 2022, 30 patients started treatment, and 24 were response-evaluable after completing ≥1 full treatment cycle. Two patients (8.3%) achieved CR, 13 (54.2%) partial response, and two (8.3%) stable disease. The CB rate was 70.8% [95% confidence interval (CI), 48.9–87.4], and the objective response rate was 62.5% (95% CI, 40.6–81.2). After 21.2-month median follow-up, median duration of response, progression-free survival, and overall survival were 9.3 (95% CI, 6.5–not available), 10.2 (95% CI, 6.0–20.1), and 13.0 months (95% CI, 9.0–not available), respectively. Twenty-three treatment-related grade ≥ 3 adverse events occurred in 12/30 patients (40%), causing treatment discontinuation in three (10%). One patient (achieving CR) had a tyrosine kinase domain mutation (p.H1094Y), and all other patients had <i>MET</i> exon 14 skipping mutations.</p>Conclusions:<p>Crizotinib is a valuable treatment option in <i>MET</i>mut aNSCLC.</p></div>