This is a Phase I, open-label, multicenter, sequential dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-e4 administered orally in subjects with advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations who have progressed following treatment with an EGFR inhibitor.
Name: ZN-e4
Description: Oral dose, tablet, daily dosingType: DrugDose escalation Dose expansion
Allocation: Non-Randomized
Sequential Assignment
There is one SNP
Inclusion Criteria: - Age ≥ 18 years - Histologically or cytologically confirmed metastatic or advanced inoperable diagnosis of non-small cell lung cancer (NSCLC) - Radiographic documentation of disease progression while on previous continuous treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) - All subjects must fulfill one of the following: 1. Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity OR 2. Must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria followed by systemic objective progression while on continuous treatment with EGFR TKI - Dose Expansion cohort(s): subjects in the dose expansion cohorts must also have confirmation of tumor T790M mutation status (confirmed positive) by cobas® EGFR Mutation Test v2 from formalin-fixed paraffin-embedded tumor tissue (FFPET) or circulating-free tumor DNA (cfDNA) plasma sample taken after disease progression on the most recent treatment regimen (EGFR TKI or chemotherapy or other therapy). --- T790M ---
ipilimumab, nivolumab, pembrolizumab, atezolizumab) within 6 months of cycle 1 day 1 - Known intermediate or strong CYP3A4 or CYP2C8 inhibitors or inducers within 14 days prior to first dose of study treatment Inclusion Criteria: - Age ≥ 18 years - Histologically or cytologically confirmed metastatic or advanced inoperable diagnosis of non-small cell lung cancer (NSCLC) - Radiographic documentation of disease progression while on previous continuous treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) - All subjects must fulfill one of the following: 1. Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity OR 2. Must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria followed by systemic objective progression while on continuous treatment with EGFR TKI - Dose Expansion cohort(s): subjects in the dose expansion cohorts must also have confirmation of tumor T790M mutation status (confirmed positive) by cobas® EGFR Mutation Test v2 from formalin-fixed paraffin-embedded tumor tissue (FFPET) or circulating-free tumor DNA (cfDNA) plasma sample taken after disease progression on the most recent treatment regimen (EGFR TKI or chemotherapy or other therapy). --- T790M ---