This is a Phase 1/2, open-label, multicenter, sequential dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ZN-e4 administered orally in subjects with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations who have progressed while on treatment with an EGFR tyrosine kinase inhibitor (TKI) agent (other lines of treatment are allowed, except for other epidermal growth factor receptor inhibitors [EGFRis]) for Phase 1; and for Phase 2, subjects who have T790M+ and are osimertinib naïve (Cohort 1), and also those who have not been treated with an EGFR Inhibitor (EGFRi) (Cohort2).
Name: ZN-e4
Allocation: Non-Randomized
Sequential Assignment
There are 3 SNPs
- Phase 1 only: Confirmation that the tumor harbors an EGFR mutation known to be associated with aberrations that are amenable to EGFRi therapy including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q. --- L858R ---
- Measurable disease meeting the criteria specified by RECIST v1.1 - Phase 2, Cohort 1 only: Subjects must have confirmation of tumor T790M mutation status (confirmed positive) and are osimertinib naïve - Phase 2, Cohort 2 only: EGFR aberrations that are amenable to EGFRi therapy, including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q, and be EGFRi naïve EXCLUSION CRITERIA - Subjects who have received only neoadjuvant or adjuvant therapy for NSCLC. --- T790M --- --- L858R ---
- Phase 1 only: Confirmation that the tumor harbors an EGFR mutation known to be associated with aberrations that are amenable to EGFRi therapy including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q. --- L858R --- --- L861Q ---
- Measurable disease meeting the criteria specified by RECIST v1.1 - Phase 2, Cohort 1 only: Subjects must have confirmation of tumor T790M mutation status (confirmed positive) and are osimertinib naïve - Phase 2, Cohort 2 only: EGFR aberrations that are amenable to EGFRi therapy, including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q, and be EGFRi naïve EXCLUSION CRITERIA - Subjects who have received only neoadjuvant or adjuvant therapy for NSCLC. --- T790M --- --- L858R --- --- L861Q ---
- Measurable disease meeting the criteria specified by RECIST v1.1 - Phase 2, Cohort 1 only: Subjects must have confirmation of tumor T790M mutation status (confirmed positive) and are osimertinib naïve - Phase 2, Cohort 2 only: EGFR aberrations that are amenable to EGFRi therapy, including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q, and be EGFRi naïve EXCLUSION CRITERIA - Subjects who have received only neoadjuvant or adjuvant therapy for NSCLC. --- T790M ---