2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.81 (Poster) REZILIENT2: Phase 2 Study of Zipalertinib in Patients With Advanced NSCLC With Exon 20 Insertions and Other Uncommon EGFR Mutations

PP01.81 (Poster) REZILIENT2: Phase 2 Study of Zipalertinib in Patients With Advanced NSCLC With Exon 20 Insertions and Other Uncommon EGFR Mutations

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REZILIENT2 is a global phase 2b study designed to evaluate the efficacy and safety of zipalertinib, an oral EGFR tyrosine kinase inhibitor (TKI), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations and other uncommon EGFR mutations. The study aims to address the unmet medical need for effective treatment options for patients with NSCLC harboring these mutations, which typically do not respond well to approved EGFR TKIs that target classical EGFR mutations.<br /><br />Zipalertinib has shown promising preclinical activity against a wide spectrum of EGFR ex20ins mutations and other uncommon EGFR mutations. In a phase 1/2a study, it demonstrated encouraging antitumor activity in heavily pretreated patients with EGFR ex20ins-mutant NSCLC, leading to the Breakthrough Therapy designation from the FDA. Therefore, the study aims to further investigate the efficacy and safety of zipalertinib in first- and later-line settings for patients with advanced NSCLC harboring EGFR ex20ins and other uncommon EGFR mutations.<br /><br />The study design includes multiple cohorts based on prior treatment and type of EGFR mutation, including patients who have progressed on systemic therapy targeting ex20ins mutations, patients who have not received prior treatment for advanced disease, patients with active central nervous system (CNS) metastases including leptomeningeal disease, and patients with other uncommon non-ex20ins EGFR mutations.<br /><br />The primary endpoint of the study is the investigator-assessed objective response rate (ORR) according to RECIST v1.1, with secondary endpoints including disease control rate, duration of response, progression-free survival, overall survival, intracranial efficacy, safety, and pharmacokinetics. Exploratory endpoints include population pharmacokinetic parameters and the association between EGFR mutations/biomarkers and safety and efficacy.<br /><br />The study is expected to be completed by October 2025, and an interim data review will be conducted to determine if each cohort meets predefined criteria for expansion. This study is sponsored by Taiho Oncology, Inc. and medical writing assistance was provided by Envision Pharma Group, funded by Taiho Oncology, Inc.

Asset Subtitle

John Heymach

Keywords

REZILIENT2

zipalertinib

EGFR tyrosine kinase inhibitor

non-small cell lung cancer

EGFR exon 20 insertion mutations

uncommon EGFR mutations

efficacy and safety

progression-free survival

overall survival

Taiho Oncology, Inc.