A Study of Azenosertib (ZN-c3) and Niraparib in Subjects With Platinum-Resistant Ovarian Cancer
A Phase 1/2 Dose-Escalation and Dose-Expansion Study of ZN-c3 in Combination With Niraparib and ZN-c3 Monotherapy in Subjects With Platinum-Resistant Ovarian Cancer
4 other identifiers
interventional
117
2 countries
22
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 ovarian-cancer
Started Jan 2022
Typical duration for phase_1 ovarian-cancer
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 8, 2021
CompletedFirst Posted
Study publicly available on registry
January 20, 2022
CompletedStudy Start
First participant enrolled
January 27, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 15, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 19, 2026
CompletedMarch 18, 2026
March 1, 2026
3.7 years
December 8, 2021
March 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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
6 months
To determine the safety and tolerability of ZN-c3 monotherapy
Frequency and severity of AEs and dose modifications
12 months
To investigate the antitumor activity of ZN-c3 monotherapy
ORR as defined by the revised RECIST Guideline version 1.1 and assessed by ICR.
12 months
Secondary Outcomes (10)
To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
30 months
To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
30 months
To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
30 months
To investigate the OS of subjects receiving ZN-c3 in combination with niraparib and ZN-c3 monotherapy
30 months
To investigate the safety and tolerability of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
30 months
- +5 more secondary outcomes
Other Outcomes (3)
To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Baseline Cyclin E expression
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
30 months
To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Changes in genomic or protein biomarkers
30 months
Study Arms (2)
Azenosertib and Niraparib
EXPERIMENTALAzenosertib in combination with Niraparib
Azenosertib
EXPERIMENTALAzenosertib Monotherapy
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- Subjects must have platinum-resistant disease.
- Must have evaluable or measurable disease according to RECIST v1.1 criterion: defined as at least one lesion that can be accurately measured.
- Adequate hematologic and organ function.
- Ability and willingness to take oral medication.
- Subjects must provide formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer.
You may not qualify if:
- 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).
- A minimum of 10 days between termination of the prior PARPi and administration of ZN-c3 and niraparib treatment is required.
- Any investigational drug therapy \<28 days.
- Prior treatment with a WEE1 inhibitor.
- Known hypersensitivity to any drugs similar to ZN-c3 and/or niraparib in class or its excipients.
- Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Uncontrolled hypertension (Diastolic BP \> 90 mmHg or Systolic BP \> 140 mmHg).
- 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).
- 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.
- 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.
- History or current evidence of congenital or family history of long QT syndrome or Torsades de Pointes (TdP).
- Taking medications with a known risk of TdP (according to current information provided at https://crediblemeds.org).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 8, 2021
First Posted
January 20, 2022
Study Start
January 27, 2022
Primary Completion
October 15, 2025
Study Completion
January 19, 2026
Last Updated
March 18, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share