Clinical trial NCT05198804: A Study of ZN-c3 and Niraparib in Subjects With Platinum-Resistant Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Platinum-resistant Ovarian Cancer
Primary Peritoneal Carcinoma
Fallopian Tube Cancer
Keywords: Wee1
Wee-1
Lead sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2022-01-20
Enrollment: 117
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Phase 1b: To investigate the safety and tolerability of ZN-c3 in combination with niraparib, including identification of the MTD and RP2D
timeFrame: 6 months
measure: Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Progression Free Survival at 4 months
timeFrame: 12 months
measure: Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Objective Response Rate
timeFrame: 18 months
measure: To determine the safety and tolerability of ZN-c3 monotherapy
timeFrame: 12 months
measure: To investigate the antitumor activity of ZN-c3 monotherapy
timeFrame: 12 months
Secondary outcomes:
measure: To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
timeFrame: 30 months
measure: To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
timeFrame: 30 months
measure: To further investigate the antitumor activity of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
timeFrame: 30 months
measure: To investigate the OS of subjects receiving ZN-c3 in combination with niraparib and ZN-c3 monotherapy
timeFrame: 30 months
measure: To investigate the safety and tolerability of ZN-c3 in combination with niraparib and ZN-c3 monotherapy
timeFrame: 30 months
measure: To evaluate changes in Patient Reported Outcomes (PROs) and quality of life
timeFrame: 30 months
measure: To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Maximum Plasma Concentration
timeFrame: 30 months
measure: 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
timeFrame: 30 months
measure: To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Trough concentration
timeFrame: 30 months
measure: To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Time to maximum plasma concentration
timeFrame: 30 months
Other outcomes:
measure: To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Baseline Cyclin E expression
timeFrame: 30 months
measure: To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Molecular determinants of sensitivity to ZN-c3
timeFrame: 30 months
measure: To investigate the PD and downstream effects of ZN-c3 when given in combination with niraparib - Changes in genomic or protein biomarkers
timeFrame: 30 months
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates (Wilmot HOPE) - USOR
state: Arizona
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health System
state: Michigan
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: Optimum Clinical Research Group- Women's Oncology
state: New Mexico
city: New York
country: United States
facility: The Blavatnik Family - Chelsea Medical Center at Mount Sinai
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Providence
country: United States
facility: Women and Infants Hospital of Rhode Island
state: Rhode Island
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Saint-Genis-Laval
country: France
facility: Centre Hospitalier Lyon Sud
city: Strasbourg
country: France
facility: ICANS - Institut de cancérologie Strasbourg Europe
city: Toulouse
country: France
facility: EDOG - Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References: