Nazartinib for treatment-naive EGFR-mutant non−small cell lung cancer: Results of a phase 2, single-arm, open-label study

Daniel S.W. Tan, Sang We Kim, Santiago Ponce Aix, Lecia V. Sequist, Egbert F. Smit, James C.H. Yang, Toyoaki Hida, Ryo Toyozawa, Enriqueta Felip, Juergen Wolf, Christian Grohé, Natasha B. Leighl, Gregory Riely, Xiaoming Cui, Mike Zou, Samson Ghebremariam, Leslie O'Sullivan-Djentuh, Riccardo Belli, Monica Giovannini, Dong Wan Kim

Research output: Contribution to journalArticlepeer-review


Introduction: Nazartinib, a novel third-generation EGFR-tyrosine kinase inhibitor, previously demonstrated antitumor activity and manageable safety in patients with EGFR-mutant advanced non−small cell lung cancer (NSCLC) who received ≤ 3 prior lines of systemic therapy. Herein, we report phase 2 efficacy and safety of first-line nazartinib. Methods: This single-arm, open-label, global study enrolled treatment-naive adult patients with stage IIIB/IV NSCLC harboring EGFR-activating mutations (eg, L858R and/or ex19del). Patients with neurologically stable and controlled brain metastases were also eligible. Patients received oral nazartinib 150 mg once daily. The primary endpoint was Blinded Independent Review Committee (BIRC)-assessed overall response rate (ORR) per RECIST v1.1. Results: Forty-five patients received ≥ 1 dose of nazartinib. The median follow-up time from enrollment to data cutoff (November 1, 2019) was 30 months (range: 25–34). The BIRC-assessed ORR was 69% (95% CI, 53–82). The median progression-free survival (PFS) was 18 months (95% CI, 15-not estimable [NE]). The median overall survival was NE. In patients with baseline brain metastases (n = 18), the ORR and median PFS (95% CIs) were 67% (41–87) and 17 months (11–21). Seventeen of 18 patients had brain metastases as non-target lesions; the CNS lesions were absent/normalized in 9 of 17 (53%). Only 2 of 27 patients without baseline brain metastases developed new brain metastases postbaseline. Most frequent adverse events (≥ 25%, any grade, all-causality) were diarrhea (47%), maculopapular rash (38%), pyrexia (29%), cough, and stomatitis (27% each). Conclusions: First-line nazartinib demonstrated promising efficacy, including clinically meaningful antitumor activity in the brain, and manageable safety in patients with EGFR-mutant NSCLC. Trial registration:

Original languageEnglish
Pages (from-to)276-286
Number of pages11
JournalEuropean Journal of Cancer
StatePublished - Sep 2022


  • EGFR
  • Nazartinib
  • Third-generation EGFR-TKI
  • Treatment-naive


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