This is a multi-part Phase 2 study to evaluate the efficacy and safety of azenosertib (ZN-c3) in subjects with Platinum-Resistant, High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Part 2 of the study will be conducted in subjects whose tumors are Cyclin E1 positive as determined by central review using the Sponsor's investigational clinical trial assay.

A Phase 2 study to evaluate the efficacy and safety of azenossertib (ZN-c3) in subjects with Platinum-Resistant, High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Azenosertib is a selective and orally bioavailable inhibitor of WEE1. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage leading to mitotic catastrophe and cancer cell death.

The study consists of two parts:

Part 1: All comers, no biomarker status required (completed enrollment)

Part 2: Cyclin E1 positive protein expression required

Inclusion Criteria:

1. Age ≥18 years

2. High-grade serous ovarian, fallopian tube or primary peritoneal cancer

3. Tumor testing (archival acceptable) confirms a positive Cyclin E1 protein status result determined by IHC using the Sponsor's investigational clinical trial assay

4. Prior therapy:

   1. Subjects must have platinum-resistant disease
   2. Parts 2a and 2b: One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
   3. Part 2c: Subjects with PROC may have 1 to 4 prior lines or regimens. Prior treatment in this cohort includes a weekly taxane regimen, either as single agent or in combination, per protocol
   4. Prior bevacizumab treatment is required, if eligible per standard of care
   5. Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
   6. Prior mirvetuximab treatment is required, if eligible per standard of care

5. Measurable disease per RECIST Version 1.1.

6. Adequate hematologic and organ function, as defined in protocol

7. ECOG 0-1

Exclusion Criteria:

1. Primary platinum-refractory disease

2. Subjects with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, low-grade, borderline, or other ovarian tumors

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

   1. Major surgery within 28 days
   2. Hospitalization within 14 days
   3. Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter);
   4. Radiation therapy within 21 days;
   5. Autologous or allogeneic stem cell transplant within 3 months.
   6. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
   7. Inability to discontinue treatment prescription or non-prescription drugs, or to discontinue consumption of food and herbal supplements that are strong or moderate CYP3A inhibitors and inducers or P-gp inhibitors at least 14 days prior to C1D1.

4. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, PKMYT1 inhibitor, or CHK1/2 inhibitor.

5. A serious illness or medical condition(s) including, but not limited to:

   1. Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible.
   2. Myocardial impairment resulting in heart failure (NYHA Class II-IV)
   3. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or may interfere with interpretation of study results
   4. Acute kidney injury requiring intervention or intravenous fluid in the last 14 days or presence of indwelling urinary catheter or percutaneous nephrostomy.
   5. 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.
   6. Active, uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral) must have completed such treatment and the infection must be considered controlled/resolved (and afebrile) by the Investigator for at least 7 days before C1D1
   7. Any evidence of 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.

6. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation).

7. Pregnant or lactating female subject or female subject of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1.

8. History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease free. Exceptions include appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, or other malignancies with an expected curative outcome.

9. Subjects who are known to be immunocompromised or HIV-positive on highly active anti-retroviral therapy.

10. Subjects with known active hepatitis B or hepatitis C infection.

11. Individuals who are judged by the Investigator to be unsuitable as study subjects.

12. Subjects who had prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.