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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03446417
Recruitment Status : Recruiting
First Posted : February 26, 2018
Last Update Posted : July 10, 2020
Sponsor:
Information provided by (Responsible Party):
Zeno Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE February 16, 2018
First Posted Date  ICMJE February 26, 2018
Last Update Posted Date July 10, 2020
Actual Study Start Date  ICMJE April 20, 2018
Estimated Primary Completion Date June 20, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2018)
Observed dose limiting toxicities [ Time Frame: 1 Cycle (21 days) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2018)
Safety and tolerability as measured by incidence of treatment emergent adverse events [ Time Frame: Through study completion, approximately 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ZN-e4 in Subjects With Epidermal Growth Factor Receptor Mutated Non-Small Cell Lung Cancer
Official Title  ICMJE 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
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE Drug: ZN-e4
Oral dose, tablet, daily dosing
Study Arms  ICMJE
  • Experimental: Phase 1
    Up to 9 sequential dose escalation cohorts to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified.
    Intervention: Drug: ZN-e4
  • 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.

    Intervention: Drug: ZN-e4
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2019)
140
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2018)
100
Estimated Study Completion Date  ICMJE December 20, 2022
Estimated Primary Completion Date June 20, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zeno Pharmaceuticals 858-263-4333 info@zenopharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03446417
Other Study ID Numbers  ICMJE ZN-e4-001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zeno Pharmaceuticals, Inc.
Study Sponsor  ICMJE Zeno Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Zeno Pharmaceuticals Zeno Pharmaceuticals
PRS Account Zeno Pharmaceuticals, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP