%0 Journal Article
%T Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer.
%A Felip E
%A Metro G
%A Soo RA
%A Wolf J
%A Solomon BJ
%A Tan DS
%A Ardizzoni A
%A Lee DH
%A Sequist LV
%A Barlesi F
%A Ponce-Aix S
%A Abreu DR
%A Campelo MRG
%A Sprauten M
%A Djentuh LO
%A Smith N
%A Jary A
%A Belli R
%A Glaser S
%A Zou M
%A Cui X
%A Giovannini M
%A Yang JC
%J Eur J Cancer
%V 208
%N 0
%D 2024 Sep 22
%M 38986421
%F 10.002
%R 10.1016/j.ejca.2024.114182
%X <B>OBJECTIVE: </B>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).<BR><B>METHODS: </B>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; EGFRL858R/ex19del; any T790M/MET); group 2 (fasted; EGFR-TKI naïve; 0-2 prior lines; de novo T790M+; any MET); group 3 (fasted; treatment-naïve; EGFRL858R/ex19del; T790M-; any MET); group 4 (with food; 0-2 prior lines; EGFRL858R/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.<BR><B>RESULTS: </B>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 %).<BR><B>CONCLUSIONS: </B>Capmatinib plus nazartinib showed antitumor activity in patients with EGFR-TKI-resistant, EGFR-mutated NSCLC. The overall safety profile was acceptable.<BR><B>BACKGROUND: </B>ClinicalTrials.gov NCT02335944.