A Phase 2 Open-Label, Multicenter Study To Evaluate Efficacy And Safety Of ZN-c3 In Subjects With High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer (DENALI / ZN-c3-005 / GOG-3066)

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

Sex: FEMALE
Minimum Age: 18 Years
Healthy Volunteers: No
Age Groups: ADULT, OLDER_ADULT

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. One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
3. Prior bevacizumab treatment is required, if eligible per standard of care
4. Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
5. 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. 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 1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation).
6. Pregnant or lactating female subject or female subject of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1.
7. 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.
8. Subjects who are known to be immunocompromised or HIV-positive on highly active anti-retroviral therapy.
9. Subjects with known active hepatitis B or hepatitis C infection.
10. Individuals who are judged by the Investigator to be unsuitable as study subjects.
11. Subjects who had prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.