Overview
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.
Description
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.
Eligibility
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:
- In the 1L setting: Complete Response, Partial Response, or Stable Disease to platinum-based chemotherapy.
- In the 2L setting:
- Progressive Disease \>183 days after receiving the last dose of platinum chemotherapy in the 1L setting,
- 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
