Capmatinib plus nazartinib in patients with EGFR-mutated non–small cell lung cancer

Enriqueta Felip, Giulio Metro, Ross A. Soo, Jürgen Wolf, Benjamin J. Solomon, Daniel SW Tan, Andrea Ardizzoni, Dae Ho Lee, Lecia V. Sequist, Fabrice Barlesi, Santiago Ponce-Aix, Delvys Rodriguez Abreu, Maria Rosario Garcia Campelo, Mette Sprauten, Leslie O.Sullivan Djentuh, Nathalie Smith, Aline Jary, Riccardo Belli, Sabine Glaser, Mike ZouXiaoming Cui, Monica Giovannini, James Chih Hsin Yang

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    Résumé

    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; 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. 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

    langue originaleAnglais
    Numéro d'article114182
    journalEuropean Journal of Cancer
    Volume208
    Les DOIs
    étatPublié - 1 sept. 2024

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