Avelumab in Combination With Lorlatinib or Crizotinib in Patients With Previously Treated Advanced NSCLC: Phase 1b/2 Results From the JAVELIN Lung 101 Trial
- Author(s)
- Solomon, BJ; Dagogo-Jack, I; Lee, SH; Boyer, MJ; Ramalingam, SS; Carcereny, E; Felip, E; Han, JY; Hida, T; Hughes, BGM; Kim, SW; Nishio, M; Seto, T; Okamoto, T; Zhang, X; Martini, JF; Wang, E; De Beukelaer, S; Bauer, TM;
- Details
- Publication Year 2024-07,Volume 5,Issue #7,Page 100685
- Journal Title
- JTO Clinical and Research Reports
- Publication Type
- Research article
- Abstract
- INTRODUCTION: The JAVELIN Lung 101 phase 1b/2 trial evaluated avelumab (immune checkpoint inhibitor) combined with lorlatinib or crizotinib (tyrosine kinase inhibitors) in ALK-positive or ALK-negative advanced NSCLC, respectively. METHODS: 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. RESULTS: In the avelumab plus lorlatinib group (ALK-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 (ALK-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). CONCLUSIONS: Avelumab plus lorlatinib treatment in ALK-positive NSCLC was feasible, but avelumab plus crizotinib treatment in ALK-negative NSCLC could not be administered at the doses tested. No evidence of increased antitumor activity was observed in either group. CLINICALTRIALSGOV IDENTIFIER: NCT02584634.
- Publisher
- Elsevier
- Keywords
- Avelumab; Crizotinib; Lorlatinib; Non–small cell lung cancer; Phase 1b/2
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.jtocrr.2024.100685
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-09-03 07:46:53
Last Modified: 2024-09-03 07:49:20