A Study of Azenosertib (ZN-c3) in Patients With Ovarian Cancer

A Phase 1b Study of ZN-c3 in Combination With Chemotherapy or Bevacizumab in Subjects With Ovarian, Peritoneal, or Fallopian Tube Cancer

This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of azenosertib (ZN-c3) in combination with other drugs.

This is a Phase 1b open-label, multicenter study evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of azenosertib (also known as ZN-c3) in combination with chemotherapy or bevacizumab. This study consists of 2 parts:

Part 1 (completed and no longer recruiting): Azenosertib in combination with chemotherapy Azenosertib was assessed in combination with chemotherapy in subjects with platinum-resistant advanced ovarian, peritoneal, or fallopian tube cancer.

Part 2: Azenosertib in combination with bevacizumab

• Dose Escalation (completed and no longer recruiting): Azenosertib was assessed in combination with bevacizumab as first-line (1L) or second-line (2L) maintenance therapy in subjects with advanced ovarian, peritoneal, or fallopian tube cancer after platinum-based chemotherapy to determine a recommended dose for expansion.
• Dose Expansion: Azenosertib will be assessed in combination with bevacizumab as 2L maintenance therapy in subjects with advanced ovarian, peritoneal, or fallopian tube cancer after platinum-based chemotherapy.

INCLUSION CRITERIA:

For Part 1:

• Histologically or cytologically confirmed FIGO Stage III/IV high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal carcinoma.
• Subjects must have received 1 or 2 prior therapeutic regimens/lines of therapy in the advanced or metastatic setting. At least one regimen must have contained cisplatin or carboplatin.
• The disease must be platinum resistant (ie, the PFI must have been < 6 months). Platinum refractory disease (ie, PD during first-line platinum-based therapy) is allowed.

For Part 2 Dose Escalation:

Prior therapy:

• Subjects must have received 6 cycles of platinum-based doublet chemotherapy in the 1L or 2L setting as their most recent therapy

Response to prior platinum therapy:

1. In the 1L setting: Complete Response, Partial Response, or Stable Disease to platinum-based chemotherapy.

2. In the 2L setting:

   1. Progressive Disease >183 days after receiving the last dose of platinum chemotherapy in the 1L setting,

   2. Complete Response, Partial Response, or Stable Disease to 2L platinum-based chemotherapy.

      • Adequate hematologic, and organ function

For Part 2 Dose Expansion:

• Subjects must have at least 4 cycles of platinum-based chemotherapy in 2L and have Complete Response, Partial Response, or Stable Disease
• Subjects must have progressed while on a PARP inhibitor for 1L maintenance Additional protocol-defined inclusion criteria may apply

EXCLUSION CRITERIA:

• Histology of abdominal adenocarcinoma of unknown origin or diagnosis of a borderline ovarian tumor.
• Subjects with carcinosarcomas (even if there is a serous component)
• A serious illness or medical condition(s)
• Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.

Additional protocol-defined exclusion criteria may apply