Brief Title
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 in Subjects With Platinum-Resistant Ovarian Cancer
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 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 in subjects with platinum-resistant ovarian
cancer who have failed Poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Phase 1: Incidence and severity of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects during Cycle 1
Secondary Outcome
To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Duration of response
Condition
Ovarian Cancer
Intervention
ZN-c3
Study Arms / Comparison Groups
ZN-c3 and Niraparib
Description: ZN-c3 in combination with Niraparib
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
138
Start Date
January 27, 2022
Completion Date
November 2023
Primary Completion Date
November 2023
Eligibility Criteria
Key Inclusion Criteria:
1. Female and at least 18 years old.
2. Histologically or cytologically confirmed recurrent high grade epithelial ovarian,
primary peritoneal, or fallopian tube cancer with histologic subtypes of serous, clear
cell or endometrial for which there is no known or established treatment available
with curative intent.
3. Have demonstrated relapse within 6 months of platinum therapy (platinum-free interval
<6 months).
4. Must have evaluable or measurable disease according to RECIST v1.1 criterion: defined
as at least one lesion that can be accurately measured.
5. Adequate hematologic and organ function.
6. Ability and willingness to take oral medication.
7. If unknown homologous recombination deficiency (HRD) status, subjects must provide
formalin-fixed, paraffin-embedded tumor samples available from the primary or
recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation.
8. Willingness to release archival tissue for research purposes or to undergo a tumor
tissue biopsy prior to dosing on Cycle 1 Day 1.
Additional Key Inclusion Criteria for Phase II:
9. This supersedes inclusion criterion 3 (above). Demonstrated relapse within 6 months of
platinum therapy, while taking a PARPi as maintenance: a minimum of 3 months is
required if the participant received PARPi maintenance following first-line
chemotherapy.
10. Must have measurable disease according to RECIST V1.1 criterion: defined as at least
one lesion that can be accurately measured.
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).
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, (858) 263-4333, [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT05198804
Organization ID
ZN-c3-006
Secondary IDs
GOG-3067
Responsible Party
Sponsor
Study Sponsor
K-Group Beta
Study Sponsor
, ,
Verification Date
October 2022