Avelumab in Combination With Lorlatinib or Crizotinib in Patients With Previously Treated Advanced NSCLC: Phase 1b/2 Results From the JAVELIN Lung 101 Trial

Abstract

<h2>Abstract</h2><h3>Introduction</h3> The JAVELIN Lung 101 phase 1b/2 trial evaluated avelumab (immune checkpoint inhibitor) combined with lorlatinib or crizotinib (tyrosine kinase inhibitors) in <i>ALK</i>-positive or <i>ALK</i>-negative advanced NSCLC, respectively. <h3>Methods</h3> Starting doses of lorlatinib 100 mg once daily or crizotinib 250 mg twice daily were administered with avelumab 10 mg/kg every 2 weeks. Primary objectives were assessment of maximum tolerated dose (MTD) and recommended phase 2 dose in phase 1 and objective response rate in phase 2. Primary end points were dose-limiting toxicity (DLT) and confirmed objective response per Response Evaluation Criteria in Solid Tumors, version 1.1. <h3>Results</h3> In the avelumab plus lorlatinib group (<i>ALK</i>-positive; n = 31; 28 in phase 1b; three in phase 2), two of 28 assessable patients (7%) had DLT, and the MTD and recommended phase 2 dose was avelumab 10 mg/kg every 2 weeks plus lorlatinib 100 mg once daily. In the avelumab plus crizotinib group (<i>ALK</i>-negative; n = 12; all phase 1b), five of 12 assessable patients (42%) had DLT, and the MTD was exceeded with avelumab 10 mg/kg every 2 weeks plus crizotinib 250 mg twice daily; alternative crizotinib doses were not assessed. Objective response rate was 52% (95% confidence interval, 33%–70%) with avelumab plus lorlatinib (complete response, 3%; partial response, 48%) and 25% (95% confidence interval, 6%–57%) with avelumab plus crizotinib (all partial responses). <h3>Conclusions</h3> Avelumab plus lorlatinib treatment in <i>ALK</i>-positive NSCLC was feasible, but avelumab plus crizotinib treatment in <i>ALK</i>-negative NSCLC could not be administered at the doses tested. No evidence of increased antitumor activity was observed in either group. <h3>ClinicalTrials.gov identifier</h3> NCT02584634