Clinical Trials/NCT05198804

NCT05198804

Completed

Phase 1

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

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc22 sites in 2 countries117 target enrollmentJanuary 27, 2022

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

InterventionsAzenosertib Niraparib

DrugsNiraparib

Overview

Phase: Phase 1
Intervention: Azenosertib
Conditions: Ovarian Cancer
Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Enrollment: 117
Locations: 22
Primary Endpoint: To investigate the antitumor activity of ZN-c3 monotherapy
Status: Completed
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

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.

Registry

clinicaltrials.gov

Start Date

January 27, 2022

End Date

January 19, 2026

Last Updated

last month

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

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

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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.
•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.

Arms & Interventions

Azenosertib

Azenosertib Monotherapy

Intervention: Azenosertib

Azenosertib and Niraparib

Azenosertib in combination with Niraparib

Intervention: Azenosertib

Azenosertib and Niraparib

Azenosertib in combination with Niraparib

Intervention: Niraparib

Outcomes

Primary Outcomes

To investigate the antitumor activity of ZN-c3 monotherapy

Time Frame: 12 months

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

To determine the safety and tolerability of ZN-c3 monotherapy

Time Frame: 12 months

Frequency and severity of AEs and dose modifications

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

Time Frame: 6 months

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

Secondary Outcomes

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)
To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Maximum Plasma Concentration(30 months)
To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Trough concentration(30 months)
To evaluate changes in Patient Reported Outcomes (PROs) and quality of life(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(30 months)
To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Time to maximum plasma concentration(30 months)
To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy(30 months)