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CompletedNCT05198804Updated Mar 18, 2026

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

A Phase 1/2 interventional study of Azenosertib and Niraparib in Ovarian Cancer, Platinum-resistant Ovarian Cancer and Primary Peritoneal Carcinoma, sponsored by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. Completed at 22 sites in 2 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-18.

Sponsored by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
117
Allocation
Non-randomized
Ages
18 Years and older
Sex
Female
01

Study summary

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 and of ZN-c3 Monotherapy in subjects with platinum-resistant ovarian cancer.

Read the 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 and of ZN-c3 Monotherapy in subjects with platinum-resistant ovarian cancer who have failed Poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment.

02

Conditions studied

  • Ovarian Cancer
  • Platinum-resistant Ovarian Cancer
  • Primary Peritoneal Carcinoma
  • Fallopian Tube Cancer

Keywords

  • Wee1
  • Wee-1
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  1. Histologically or cytologically confirmed recurrent high grade epithelial ovarian, primary peritoneal, or fallopian tube cancer with histologic subtypes of serous, clear cell or endometroid for which there is no known or established treatment available with curative intent.
  2. Subjects must have platinum-resistant disease.
  3. Must have evaluable or measurable disease according to RECIST v1.1 criterion: defined as at least one lesion that can be accurately measured.
  4. Adequate hematologic and organ function.
  5. Ability and willingness to take oral medication.
  6. Subjects must provide formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer.

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).
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
117 participants (actual)

Study arms

  • Experimental
    Azenosertib and Niraparib

    Azenosertib in combination with Niraparib

    Drug: Azenosertib · Drug: Niraparib

  • Experimental
    Azenosertib

    Azenosertib Monotherapy

    Drug: Azenosertib

Interventions

  • DrugAzenosertib

    Azenosertib

    Also known as: ZN-c3

  • DrugNiraparib

    Niraparib

05

What researchers measure

Primary outcomes

  1. To investigate the safety and tolerability of ZN-c3 in combination with niraparib, including identification of the MTD and RP2D

    Incidence and severity of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects during Cycle 1

    Time frame: 6 months

  2. To determine the safety and tolerability of ZN-c3 monotherapy

    Frequency and severity of AEs and dose modifications

    Time frame: 12 months

  3. To investigate the antitumor activity of ZN-c3 monotherapy

    ORR as defined by the revised RECIST Guideline version 1.1 and assessed by ICR.

    Time frame: 12 months

Secondary outcomes

  1. To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy

    Duration of response (DOR) as key secondary endpoint

    Time frame: 30 months

  2. To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy

    Clinical Benefit Rate (CBR), Progression Free Survival (PFS) (median and 4-month rate), as defined by the revised RECIST version 1.1

    Time frame: 30 months

  3. To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy

    Objective Response Rate (ORR) based on investigator assessment

    Time frame: 30 months

  4. To investigate the OS of subjects receiving ZN-c3 in combination with niraparib and ZN-c3 monotherapy

    OS (median and at 12 months)

    Time frame: 30 months

  5. To investigate the safety and tolerability of ZN-c3 in combination with niraparib and ZN-c3 monotherapy

    Frequency and severity of AEs and dose modifications

    Time frame: 30 months

  6. To evaluate changes in Patient Reported Outcomes (PROs) and quality of life

    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

    Time frame: 30 months

  7. To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Maximum Plasma Concentration

    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

    Time frame: 30 months

  8. 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

    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

    Time frame: 30 months

  9. To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Trough concentration

    Trough concentration \[Ctrough\] of ZN-c3 (and its potential metabolites, as applicable) and niraparib (and their potential metabolites, as applicable) will be determined

    Time frame: 30 months

  10. To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Time to maximum plasma concentration

    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

    Time frame: 30 months

Other outcomes

  1. To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Baseline Cyclin E expression

    Baseline Cyclin E expression in pre-dose tumor tissue

    Time frame: 30 months

  2. To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Molecular determinants of sensitivity to ZN-c3

    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)

    Time frame: 30 months

  3. To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Changes in genomic or protein biomarkers

    Changes in genomic or protein biomarkers in peripheral blood samples

    Time frame: 30 months

06

Study locations

22 sites
  • Arizona Oncology Associates (Wilmot HOPE) - USOR
    Tucson, Arizona 85711, United States
  • Rocky Mountain Cancer Centers
    Aurora, Colorado 80012, United States
  • University of Colorado
    Aurora, Colorado 80045, United States
  • Mount Sinai Comprehensive Cancer Center
    Miami Beach, Florida 33140, United States
  • Karmanos Cancer Institute
    Detroit, Michigan 48201, United States
  • Spectrum Health System
    Grand Rapids, Michigan 49503, United States
  • Rutgers New Jersey Medical School
    Newark, New Jersey 07103, United States
  • Optimum Clinical Research Group- Women's Oncology
    Albuquerque, New Mexico 87109, United States
  • The Blavatnik Family - Chelsea Medical Center at Mount Sinai
    New York, New York 10011, United States
  • Willamette Valley Cancer Institute and Research Center
    Eugene, Oregon 97401, United States
  • Women and Infants Hospital of Rhode Island
    Providence, Rhode Island 02905, United States
  • Texas Oncology-Fort Worth Cancer Center
    Fort Worth, Texas 76104, United States
  • MD Anderson Cancer Center, Gynecologic Oncology Center
    Texas City, Texas 77030, United States
  • University of Virginia
    Charlottesville, Virginia 22908, United States
  • Virginia Cancer Specialists
    Fairfax, Virginia 22031, United States
  • Virginia Commonwealth University
    Richmond, Virginia 23298, United States
  • Centre Georges François Leclerc
    Dijon, France
  • Centre Oscar Lambret
    Lille, France
  • Centre Hospitalier Lyon Sud
    Saint-Genis-Laval, France
  • ICANS - Institut de cancérologie Strasbourg Europe
    Strasbourg, France
  • EDOG - Institut Claudius Regaud
    Toulouse, France
  • Institut Gustave Roussy
    Villejuif, France
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT05198804
Lead sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Responsible party
Sponsor
First posted
Jan 20, 2022
Start date
Jan 27, 2022
Primary completion
Oct 15, 2025
Completion
Jan 19, 2026
Last update
Mar 18, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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