Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies

Lung Cancer. 2023 Jun:180:107194. doi: 10.1016/j.lungcan.2023.107194. Epub 2023 Apr 17.

Abstract

Background: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here.

Methods: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated.

Results: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months.

Conclusions: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

Trial registration: ClinicalTrials.gov NCT03386955 NCT03812809.

Keywords: BPI-7711; CNS; EGFR T790M mutation; NSCLC; Rezivertinib.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / therapeutic use
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Central Nervous System / pathology
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • EGFR protein, human
  • ErbB Receptors
  • Protein Kinase Inhibitors
  • rezivertinib

Associated data

  • ClinicalTrials.gov/NCT03386955
  • ClinicalTrials.gov/NCT03812809