GOG 3066 Eligibility Criteria
An individual must meet all of the following criteria in order to participate in this study:
1. Provision of signed informed consent (obtained according to institutional guidelines) prior to initiation of any study-related procedures.
2. Age ≥18 years at the time of informed consent.
3. Histologically or cytologically confirmed recurrent, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer with copy number amplification in the CCNE1 gene determined from CLIA-approved (or country-specific equivalent) prior genomic profiling, as reviewed and approved by the Sponsor.
4. Prior therapy:
a. Subject must have documented progressive disease ≤6 months (183 days) from last dose of platinum therapy, and must not have platinum refractory disease (ie, disease progression during first-line platinum therapy).
b. Subjects must have received at least 1 but no more than 4 prior systemic lines of anticancer therapy if being enrolled to Part 2 (or no more than 5 if being enrolled to Part 1b)
c. Prior bevacizumab treatment is required, unless medically contraindicated based on Investigator review.
5. Subject must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors Guideline Version 1.1 (RECIST v1.1).
6. Performance status: Eastern Cooperative Oncology Group (ECOG) score of ≤1.
7. Adequate hematologic and organ function during the Screening Period, as defined by the following criteria:
a. Absolute neutrophil count (ANC) ≥1.5 × 109 /L.
b. Platelet count ≥100 × 109 /L; excluding measurements obtained within 3 days after transfusion of platelets.
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastases, AST and ALT ≤5 × ULN.
d. Total serum bilirubin ≤1.5 × ULN or ≤3 × ULN in the case of Gilbert’s syndrome.
e. Creatinine clearance (CrCl) ≥30 mL/min based on Cockcroft-Gault method.
8. Subject must agree to provide a mandatory formalin-fixed paraffin-embedded (FFPE) tumor sample collected within 2 years from Cycle 1 Day 1 (C1D1), or to undergo a fresh
9. Females of childbearing potential must agree to use an effective method of contraception prior to the first dose and for at least 6 months after the last dose of ZN-c3. Male subjects must agree to use an effective method of contraception prior to the first dose and for at least 3 months after the last dose of ZN-c3. For determination of effective methods of contraception, refer to Section 10.2.
10. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Individuals meeting the following exclusion criteria will be excluded from this study:
1. Any of the following treatment interventions within the specified time frame prior to C1D1:
a. Major surgery within 28 days (any surgical incision should be fully healed prior to
study drug administration).
b. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter).
c. Radiation therapy within 21 days; however, if the radiation portal covered ≤5% of the bone marrow, the subject is eligible irrespective of the end date of radiotherapy.
d. Autologous or allogeneic stem cell transplant within 3 months.
e. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
f. Inability to discontinue treatment prescription or non-prescription drugs, or to discontinue consumption of food and herbal supplements that are strong and moderate CYP3A inhibitors and inducers or P-gp inhibitors at least 14 days prior to C1D1.
2. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor.
3. Known hypersensitivity to any inactive ingredients present in ZN-c3.
4. A serious illness or medical condition(s) including, but not limited to, the following:
a. Brain metastases that require immediate treatment or are clinically or radiologically unstable (ie, have been stable for <1 month). If receiving corticosteroids for treatment of brain metastases, subjects must receive a stable or decreasing dose for at least 1 week before enrollment. (Note: Subjects with asymptomatic brain metastases, or subjects with primary central nervous system tumors, are eligible to participate in the study.)
b. Leptomeningeal disease that requires or is anticipated to require immediate treatment.
c. Myocardial impairment of any cause (eg, 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).
d. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the subject inappropriate for entry into this study.
e. Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for intravenous 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.
f. Active or uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral treatment) must have completed such treatment and the infection must be considered controlled/resolved by the Investigator before enrollment.
g. Any evidence of small bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for small bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.
5. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation).
6. Pregnant or lactating female or female of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1.
7. Subject with active (uncontrolled, metastatic) second malignancies or requiring therapy.
8. Individuals who are judged by the Investigator to be unsuitable as study subjects.