A Study of ZN-e4 in Subjects With Epidermal Growth Factor Receptor Mutated Non-Small Cell Lung Cancer

A Phase 1/2 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of ZN-e4 (KP-673) in Patients With Advanced Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor (EGFR) Mutations

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).

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: ZN-e4

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina
    • Site 8
  • Sarajevo, Bosnia and Herzegovina
    • Site 7
• United States
  • California
    • Duarte, California, United States, 91010
      • Site 2
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Site 5
  • New York
    • East Setauket, New York, United States, 11733
      • Site 1
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Site 6
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Site 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

• Age ≥ 18 years
• Histologically or cytologically confirmed metastatic or advanced inoperable diagnosis of NSCLC
• Documented radiographic progression on the last treatment administered prior to enrolling in the study.
• 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. OR - Must have experienced clinical benefit from an EGFRi,
• All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 or baseline before the start of study drug dosing (with the exception of alopecia [any grade permitted] and neurotoxicity [Grade 1 or 2 permitted]).
• 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.
• Phase 1 only: Treatment with an EGFRi within 7 days or 5 half-lives of the first dose of study treatment, whichever is shorter.
• Phase 1 only: Cytotoxic chemotherapy, investigational agents, or any anticancer therapy for the treatment of advanced NSCLC (other than EGFRi) within 21 days of the first dose of study treatment.
• Prior treatment with immunotherapy within 3 months prior to the first dose of study treatment.
• Radiotherapy within 28 days of first dose of study treatment; subjects given palliative radiotherapy to peripheral sites (e.g., bone metastases) may enter the study before 28 days have elapsed provided the radiated sites do not contain lesions which may be used to evaluate response, and must have recovered from any acute, reversible effects.
• Known or suspected central nervous system (CNS) metastases or leptomeningeal disease (Phase 1 only). Subjects with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy, does not have brain metastasis related symptoms, is not requiring systemic steroids for at least 2 weeks prior to study drug administration, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 2 weeks prior to study drug administration.
• Prior allogeneic bone marrow transplantation.
• History of a concurrent or second malignancy except for: adequately treated local basal cell or squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder cancer; breast carcinoma in situ; adequately treated Stage 1 or 2 cancer currently in complete remission; any other cancer that has been in complete remission for ≥5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; Up to 9 sequential dose escalation cohorts to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified.	Drug: ZN-e4; Oral dose, tablet, daily dosing
Experimental: Phase 2; MTD/RP2D in subjects: Cohort 1: with T790M mutation in epidermal growth factor receptor (EGFR) gene, and are osimertinib naïve. Cohort 2: EGFRm amenable to EGFR inhibitor therapy (eg, exon 19 del, L858R) and who have never been treated with EGFRis.	Drug: ZN-e4; Oral dose, tablet, daily dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Observed dose limiting toxicities	1 Cycle (21 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability as measured by incidence of treatment emergent adverse events	Through study completion, approximately 2 years

Collaborators and Investigators

• Sponsor: Zeno Pharmaceuticals, Inc.
• Investigators: Study Director: Zeno Pharmaceuticals, Zeno Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2018
• Primary Completion (Actual): January 17, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: February 16, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ZN-e4-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No