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

ID: NCT03446417
Status: Not yet recruiting
Phase: Phase 1
Start Date: March 01, 2018
First Submitted: February 16, 2018
Last Updated: February 22, 2018
Results: N/A
Sponsors & Collaborators: Zeno Pharmaceuticals, Inc.
Location: United States
Conditions: Carcinoma, Non-Small-Cell Lung
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Study Description

Brief Summary

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.

Detailed Description

Condition or disease Intervention/treatment Phase

Carcinoma, Non-Small-Cell Lung

Drug: ZN-e4
Other Names
Phase 1

Tracking Information

First Submitted DateFebruary 16, 2018
Last Update Posted DateFebruary 22, 2018
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateDecember 01, 2020
Anticipated Primary Completion DateMarch 01, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Observed dose limiting toxicities [Time Frame: 1 Cycle (21 days)]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Safety and tolerability as measured by incidence of treatment emergent adverse events [Time Frame: Through study completion, approximately 2 years]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of ZN-e4 in Subjects With Epidermal Growth Factor Receptor Mutated Non-Small Cell Lung Cancer
Official TitleA Phase 1 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of ZN-e4 in Patients With Advanced Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor (EGFR) Mutations
Brief Summary

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.

Detailed Description

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
100
Allocation
Non-Randomized
Interventional Model
Sequential Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Carcinoma, Non-Small-Cell Lung
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: ZN-e4

Oral dose, tablet, daily dosing

Other Names
Study Groups/Cohorts
Dose escalation
Up to 6 sequential dose escalation cohorts until maximum tolerated dose or recommended phase 2 dose is identified

Dose expansion
ZN-e4 in subjects with T790M mutation in epidermal growth factor receptor (EGFR) gene.

Study Arms
Experimental Dose escalation
Up to 6 sequential dose escalation cohorts until maximum tolerated dose or recommended phase 2 dose is identified
Drug : ZN-e4
Oral dose, tablet, daily dosing

Experimental Dose expansion
ZN-e4 in subjects with T790M mutation in epidermal growth factor receptor (EGFR) gene.
Drug : ZN-e4
Oral dose, tablet, daily dosing

Arm Intervention/Treatment
Experimental Dose escalation
Up to 6 sequential dose escalation cohorts until maximum tolerated dose or recommended phase 2 dose is identified
Drug : ZN-e4
Experimental Dose expansion
ZN-e4 in subjects with T790M mutation in epidermal growth factor receptor (EGFR) gene.
Drug : ZN-e4

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment100
Completion DateDecember 01, 2020
Eligibility Criteria: 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).

Exclusion Criteria:
- Treatment with an EGFR TKI within 10 days or 5 half-lives of the first dose of study treatment, whichever is longer
- Dose Expansion cohorts: Prior treatment with osimertinib (Tagrisso®). Prior treatment with osimertinib (Tagrisso®) is allowed for subjects participating in the dose escalation portion of the study
- Cytotoxic chemotherapy, investigational agents, or any anticancer therapy for the treatment of advanced NSCLC (other than EGFR TKI) within 21 days of the first dose of study treatment
- Prior treatment with immunotherapy (e.g. 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
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT03446417
Other Study ID Numbers
ZN-e4-001
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Zeno Pharmaceuticals, Inc.
Collaborators
Not Available
Investigators
Not Available