Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer.
Journal
European journal of cancer (Oxford, England : 1990)
Journal Volume
208
Start Page
論文號碼 114182
ISSN
1879-0852
Date Issued
2024-09
Author(s)
Felip, Enriqueta
Metro, Giulio
Soo, Ross A
Wolf, Jürgen
Solomon, Benjamin J
Tan, Daniel Sw
Ardizzoni, Andrea
Lee, Dae Ho
Sequist, Lecia V
Barlesi, Fabrice
Ponce-Aix, Santiago
Abreu, Delvys Rodriguez
Campelo, Maria Rosario Garcia
Sprauten, Mette
Djentuh, Leslie O'Sullivan
Smith, Nathalie
Jary, Aline
Belli, Riccardo
Glaser, Sabine
Zou, Mike
Cui, Xiaoming
Giovannini, Monica
Abstract
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).
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; any T790M/MET); group 2 (fasted; EGFR-TKI naïve; 0-2 prior lines; de novo T790M+; any MET); group 3 (fasted; treatment-naïve; EGFR; T790M-; any MET); group 4 (with food; 0-2 prior lines; EGFR; 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.
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 %).
Capmatinib plus nazartinib showed antitumor activity in patients with EGFR-TKI-resistant, EGFR-mutated NSCLC. The overall safety profile was acceptable.
ClinicalTrials.gov NCT02335944.
Subjects
Capmatinib
EGFR
MET
NSCLC
Nazartinib
SDGs
Type
journal article