A Study of ZN-c3 and Niraparib in Subjects With Platinum-Resistant Ovarian Cancer

June 16, 2023 updated by: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

A Phase 1/2 Dose-Escalation and Dose-Expansion Study of ZN-c3 in Combination With Niraparib in Subjects With Platinum-Resistant Ovarian Cancer

This is a Phase 1/2 study to evaluate the safety, clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD) of ZN-c3 in combination with niraparib in subjects with platinum-resistant ovarian cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1/2 open-label, multicenter study to evaluate the safety, clinical activity, PK, and PD of ZN-c3 in combination with niraparib in subjects with platinum-resistant ovarian cancer who have failed Poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment.

Study Type

Interventional

Enrollment (Estimated)

138

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Dijon, France
        • Recruiting
        • Centre Georges Francois Leclerc
        • Contact:
          • Meryem Erman
          • Phone Number: 3890 +33 3 80 73 75 00
          • Email: merman@cgfl.fr
        • Contact:
          • Magali Arnaud
          • Phone Number: 3210 +33 3 80 73 75 00
          • Email: MArnaud@cgfl.fr
      • Lille, France
      • Saint-Genis-Laval, France
      • Strasbourg, France
        • Recruiting
        • ICANS - Institut de cancérologie Strasbourg Europe
        • Contact:
        • Contact:
      • Toulouse, France
      • Villejuif, France
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85711
        • Recruiting
        • Arizona Oncology Associates (Wilmot HOPE) - USOR
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
      • Aurora, Colorado, United States, 80012
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Contact:
      • Grand Rapids, Michigan, United States, 49503
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Recruiting
        • Rutgers New Jersey Medical School
        • Contact:
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Recruiting
        • Optimum Clinical Research Group- Women's Oncology
        • Contact:
    • New York
      • New York, New York, United States, 10011
        • Recruiting
        • The Blavatnik Family - Chelsea Medical Center at Mount Sinai
        • Contact:
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Willamette Valley Cancer Institute and Research Center
        • Contact:
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Recruiting
        • Women and Infants Hospital of Rhode Island
        • Contact:
    • Texas
      • Fort Worth, Texas, United States, 76104
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia
        • Contact:
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. Female and at least 18 years old.
  2. Histologically or cytologically confirmed recurrent high grade epithelial ovarian, primary peritoneal, or fallopian tube cancer with histologic subtypes of serous, clear cell or endometrial for which there is no known or established treatment available with curative intent.
  3. Have demonstrated relapse within 6 months of platinum therapy (platinum-free interval <6 months).
  4. Must have evaluable or measurable disease according to RECIST v1.1 criterion: defined as at least one lesion that can be accurately measured.
  5. Adequate hematologic and organ function.
  6. Ability and willingness to take oral medication.
  7. If unknown homologous recombination deficiency (HRD) status, subjects must provide formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation.

  8. Willingness to release archival tissue for research purposes or to undergo a tumor tissue biopsy prior to dosing on Cycle 1 Day 1.

    Additional Key Inclusion Criteria for Phase II:

  9. This supersedes inclusion criterion 3 (above). Demonstrated relapse within 6 months of platinum therapy, while taking a PARPi as maintenance: a minimum of 3 months is required if the participant received PARPi maintenance following first-line chemotherapy.
  10. Must have measurable disease according to RECIST V1.1 criterion: defined as at least one lesion that can be accurately measured.

Key Exclusion Criteria:

  1. Prior therapy directed at the malignant tumor within the last four weeks prior to Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin C).
  2. A minimum of 10 days between termination of the prior PARPi and administration of ZN-c3 and niraparib treatment is required.
  3. Any investigational drug therapy <28 days.
  4. Prior treatment with a WEE1 inhibitor.
  5. Known hypersensitivity to any drugs similar to ZN-c3 and/or niraparib in class or its excipients.
  6. Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  7. Uncontrolled hypertension (Diastolic BP > 90 mmHg or Systolic BP > 140 mmHg).
  8. Myocardial impairment of any cause (e.g., cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV).
  9. Significant gastrointestinal abnormalities, requirement for IV alimentation, active peptic ulcer, chronic diarrhea, or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption.
  10. 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of >480 ms, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid.
  11. History or current evidence of congenital or family history of long QT syndrome or Torsades de Pointes (TdP).
  12. Taking medications with a known risk of TdP (according to current information provided at https://crediblemeds.org).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ZN-c3 and Niraparib
ZN-c3 in combination with Niraparib
Drug: ZN-c3
ZN-c3 will be administered.
Drug: Niraparib
Niraparib will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Incidence and severity of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects during Cycle 1
Time Frame: 6 months
Phase 1: To investigate the safety and tolerability of ZN-c3 in combination with niraparib, including identification of the MTD and RP2D
6 months
Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Progression Free Survival at 4 months
Time Frame: 12 months
Stage 1 (Futility): Progression-Free Survival at 4 months (PFS@4) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1
12 months
Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Objective Response Rate
Time Frame: 18 months
Stage 2 (Promising Clinical Activity): Objective response rate (ORR) as defined by the revised RECIST Guideline version 1.1 and assessed by Independent Central Review (ICR)
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Duration of response
Time Frame: 30 months
Duration of response (DOR) as key secondary endpoint
30 months
To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Clinical Benefit Rate
Time Frame: 30 months
Clinical Benefit Rate (CBR), Progression Free Survival (PFS) (median and 4-month rate), as defined by the revised RECIST version 1.1
30 months
To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Objective Response Rate
Time Frame: 30 months
Objective Response Rate (ORR) based on investigator assessment
30 months
To investigate the OS of subjects receiving ZN-c3 in combination with niraparib
Time Frame: 30 months
OS (median and at 12 months)
30 months
To investigate the safety and tolerability of ZN-c3 in combination with niraparib
Time Frame: 30 months
Frequency and severity of AEs, including laboratory abnormalities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
30 months
To evaluate changes in Patient Reported Outcomes (PROs) and quality of life
Time Frame: 30 months
Ongoing measurement of subject-reported symptomatic toxicity according to the PRO-CTCAE, and determination of change from Baseline in self-reported quality of life using EQ-5D-5L
30 months
To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Maximum Plasma Concentration
Time Frame: 30 months
The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined
30 months
To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Area under the plasma concentration-time curve from 0 to 24h
Time Frame: 30 months
Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined
30 months
To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Trough concentration
Time Frame: 30 months
Trough concentration [Ctrough] of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined
30 months
To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Time to maximum plasma concentration
Time Frame: 30 months
Time to maximum plasma concentration (Tmax) of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined
30 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Baseline Cyclin E expression
Time Frame: 30 months
Baseline Cyclin E expression in pre-dose tumor tissue
30 months
To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Molecular determinants of sensitivity to ZN-c3
Time Frame: 30 months
Molecular determinants of sensitivity to ZN-c3 including but not limited to Baseline DNA Damage Repair (DDR) gene mutations, deletions, copy number variations or indices of genetic instability in either tumor tissue or cell-free DNA (cfDNA)
30 months
To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Changes in genomic or protein biomarkers
Time Frame: 30 months
Changes in genomic or protein biomarkers in peripheral blood samples
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 27, 2022

Primary Completion (Estimated)

November 1, 2023

Study Completion (Estimated)

November 1, 2023

Study Registration Dates

First Submitted

December 8, 2021

First Submitted That Met QC Criteria

January 6, 2022

First Posted (Actual)

January 20, 2022

Study Record Updates

Last Update Posted (Estimated)

June 19, 2023

Last Update Submitted That Met QC Criteria

June 16, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZN-c3-006
  • GOG-3067 (Other Identifier: GOG)
  • 2021-004161-13 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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