Lorlatinib for Previously Treated ALK-Positive Advanced NSCLC: Primary Efficacy and Safety From a Phase 2 Study in People's Republic of China

J Thorac Oncol. 2022 Jun;17(6):816-826. doi: 10.1016/j.jtho.2022.02.014. Epub 2022 Mar 17.

Abstract

Introduction: Lorlatinib was found to have activity in ALK-positive NSCLC in a global phase 1 and 2 study. We report an ongoing phase 2 study in Chinese patients with ALK-positive advanced or metastatic NSCLC.

Methods: Open-label, dual-cohort study (NCT03909971); patients had progressive disease after ALK tyrosine kinase inhibitor treatment (cohort 1: previous crizotinib; cohort 2: one ALK tyrosine kinase inhibitor other than crizotinib [±prior crizotinib]), more than or equal to one unirradiated extracranial target lesion, and Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received oral lorlatinib 100 mg once daily in continuous 21-day cycles. Primary end point: objective response in cohort 1 by independent central radiology (ICR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Analyses were based on patients receiving more than or equal to one dose.

Results: At data cutoff (August 10, 2020), 109 patients were enrolled (cohort 1: n = 67; cohort 2: n = 42). A total of 47 patients in cohort 1 (70.1%, 95% confidence interval [CI]: 57.7-80.7, p < 0.0001; primary end point) and 20 patients in cohort 2 (47.6%, 95% CI: 32.0-63.6, secondary end point) achieved objective response by ICR. Median progression-free survival was not reached in cohort 1 and was 5.6 months in cohort 2. In patients with brain lesions at baseline, 29 of 36 patients in cohort 1 (80.6%, 95% CI: 64.0-91.8) and 10 of 21 patients in cohort 2 (47.6%, 95% CI: 25.7-70.2) achieved objective intracranial response by ICR. Hypercholesterolemia (92.7%) and hypertriglyceridemia (90.8%) (cluster terms) were common treatment-related adverse events (TRAEs). Nine patients (8.3%) had serious TRAEs; one permanently discontinued from treatment because of TRAEs.

Conclusions: Lorlatinib was found to have a robust and durable response and high intracranial objective response in previously treated Chinese patients with ALK-positive NSCLC.

Keywords: ALK; China; Lorlatinib; Non–small cell lung cancer; Tyrosine kinase inhibitor.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aminopyridines / adverse effects
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cohort Studies
  • Crizotinib / therapeutic use
  • Humans
  • Lactams / adverse effects
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Protein Kinase Inhibitors / adverse effects
  • Pyrazoles / adverse effects
  • Receptor Protein-Tyrosine Kinases
  • Taiwan

Substances

  • Aminopyridines
  • Lactams
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Crizotinib
  • Receptor Protein-Tyrosine Kinases
  • lorlatinib