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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
117
Azenosertib
Niraparib
Arizona Oncology Associates (Wilmot HOPE) - USOR
Tucson, Arizona, United States
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
To determine the safety and tolerability of ZN-c3 monotherapy
Frequency and severity of AEs and dose modifications
Time frame: 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.
Time frame: 12 months
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
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
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
To investigate the OS of subjects receiving ZN-c3 in combination with niraparib and ZN-c3 monotherapy
OS (median and at 12 months)
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Rocky Mountain Cancer Centers
Aurora, Colorado, United States
University of Colorado
Aurora, Colorado, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Spectrum Health System
Grand Rapids, Michigan, United States
Rutgers New Jersey Medical School
Newark, New Jersey, United States
Optimum Clinical Research Group- Women's Oncology
Albuquerque, New Mexico, United States
The Blavatnik Family - Chelsea Medical Center at Mount Sinai
New York, New York, United States
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, United States
...and 12 more locations
Time frame: 30 months
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
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
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
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
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
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