A Study of ZN-c3 in Subjects With High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer

This is an interventional treatment trial for High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer Read More

Inclusion Criteria:

1. Age ≥18 years at the time of informed consent.
2. Histologically or cytologically confirmed recurrent, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer with copy number amplification in the CCNE1 gene

3. Prior therapy:

   1. Documented progressive disease ≤6 months
   2. One to 3 prior lines or regimens are allowed
   3. Prior bevacizumab treatment is required
4. Subjects must have at least one measurable lesion as defined by RECIST Guideline Version 1.1.
5. Performance Status: Eastern Cooperative Oncology Group (ECOG) score of ≤1.
6. Adequate hematologic and organ function
7. Females of childbearing potential and male subjects must agree to use an effective method of contraception prior to the first dose and for 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.
8. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. 1. Any of the following treatment interventions within the specified time frame prior to C1D1:

   1. Major surgery within 28 days (any surgical incision should be fully healed prior to study drug administration);
   2. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter);
   3. 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.
   4. Autologous or allogeneic stem cell transplant within 3 months.
   5. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
   6. Inability to discontinue treatment prescription or non-prescription drugs, or to discontinue consumption of food and herbal supplements, that are strong/ and moderate CYP3A4 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)
5. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation).
6. Pregnant or lactating females or females of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1.
7. Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
8. Individuals who are judged by the Investigator to be unsuitable as study subjects.
9. 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of >470 ms, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid.
10. History or current evidence of congenital or family history of long QT syndrome or Torsade de Pointes (TdP).