Phase 3 Study of Azenosertib Versus Chemotherapy in Platinum-Resistant Ovarian Cancers Positive for Cyclin E1 Protein Expression

Prior treatment

• Any of the following treatment interventions within the specified time frame before randomization: a. Hospitalization for any reason within 14 days b. Major surgery within 28 days before randomization and any preplanned major surgery scheduled during the study treatment period c. Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives d. 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 e. Autologous or allogeneic stem cell transplant within 3 months f. Current use of any other investigational drug therapy < 28 days or 5 half-lives
• Inability to discontinue treatment with prescription or nonprescription drugs that are specified in the protocol.
• Inability to discontinue any of the following: a. consumption of food and herbal supplements specified in the protocol at least 14 days before C1D1 b. ongoing requirement for (or anticipated future need of) a prohibited therapy, food, or supplement
• Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or PKMYT1 inhibitor.
• Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade ≤ 2 neuropathy, alopecia, or skin pigmentation). For the complete Exclusion Criteria, please refer to the study protocol

Other illness

• Platinum refractory disease (in front line therapy)
• A serious illness or medical conditions, listed in study protocol

Other

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

• Pre-screening Inclusion criteria: Provision of evaluable, most recent FFPE tumor tissue block (preferably collected within the previous 3 years; if multiple tissue blocks are available, the most recently collected tissue sample is to be submitted) or 15 serially sectioned slides freshly cut from an FFPE block.
• Prior mirvetuximab is required if approved and available for eligible subjects
• Adequate hematologic and organ function during the Screening Period For the complete Inclusion Criteria, please refer to the study protocol
• Provision of signed Main ICF
• Female Age ≥18 years (or age of majority in local region) at the time of informed consent.
• Performance status: Eastern Cooperative Oncology Group (ECOG) score of ≤ 1
• Histologically or cytologically diagnosed high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer
• Subjects must have at least one measurable lesion as defined by RECIST Guideline Version 1.1
• The subject’s tumor tissue must be positive for cyclin E1 protein expression per the Sponsor’s clinically validated, in vitro diagnostic assay
• Subject must have platinum-resistant disease
• Subjects must have received 1-3 prior lines of therapy (up to 4 if prior mirvetuximab )