Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer
- Author(s)
- Felip, E; Metro, G; Soo, RA; Wolf, J; Solomon, BJ; Tan, DS; Ardizzoni, A; Lee, DH; Sequist, LV; Barlesi, F; Ponce-Aix, S; Abreu, DR; Campelo, MRG; Sprauten, M; Djentuh, LO; Smith, N; Jary, A; Belli, R; Glaser, S; Zou, M; Cui, X; Giovannini, M; Yang, JC;
- Journal Title
- European Journal of Cancer
- Publication Type
- Research article
- Abstract
- PURPOSE: This phase 1b/2 trial evaluated the efficacy and safety of capmatinib plus nazartinib in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). METHODS: In phase 1b, patients with progression on first-/second-generation EGFR-TKIs received escalating doses of capmatinib 200-400 mg bid plus nazartinib 50-150 mg qd. Once the MTD/RP2D was declared, phase 2 commenced with patient enrollment into groups according to mutation status and prior lines of treatment: group 1 (fasted; EGFR-TKI resistant; 1-3 prior lines; EGFR(L858R/ex19del); any T790M/MET); group 2 (fasted; EGFR-TKI naïve; 0-2 prior lines; de novo T790M+; any MET); group 3 (fasted; treatment-naïve; EGFR(L858R/ex19del); T790M-; any MET); group 4 (with food; 0-2 prior lines; EGFR(L858R/ex19del); any T790M/MET). Primary endpoints in phase 2 were investigator-assessed overall response rate (ORR) per RECIST v1.1 (groups 1-3), safety, and tolerability of the combination with food (group 4). Efficacy was assessed by T790M and MET status for a subgroup of patients. RESULTS: The RP2D was capmatinib 400 mg bid plus nazartinib 100 mg qd. In phase 2 (n = 144), the ORR was 28.8 %, 33.3 %, 61.7 %, and 42.9 % in groups 1 (n = 52), 2 (n = 3), 3 (n = 47), and 4 (n = 42), respectively. In group 1 +phase 1b RP2D, the ORR was 45.8 %, 26.2 %, 37.9 %, and 32.4 % in MET+ (n = 24), MET- (n = 42), T790M+ (n = 29), and T790M- (n = 34) patients. Most common any-grade treatment-related adverse events (≥25 %; n = 144) were peripheral edema (54.9 %), nausea (41.7 %), diarrhea (34.0 %), and maculopapular rash (25.0 %). CONCLUSION: Capmatinib plus nazartinib showed antitumor activity in patients with EGFR-TKI-resistant, EGFR-mutated NSCLC. The overall safety profile was acceptable. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02335944.
- Publisher
- Elsevier
- Keywords
- Capmatinib; Egfr; Met; Nsclc; Nazartinib
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2024.114182
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-01 04:52:55
Last Modified: 2024-08-01 05:00:54