Solid Tumor, Epithelial Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
Conditions
Keywords
Solid Tumor
Brief summary
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.
Detailed 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.
Interventions
DRUGAzenosertib
Investigational drug
DRUGCarboplatin
Carboplatin is an approved drug
DRUGPegylated liposomal doxorubicin
Pegylated liposomal doxorubicin (PLD) is an approved drug
DRUGPaclitaxel
Paclitaxel is an approved drug
DRUGGemcitabine
Gemcitabine is an approved drug
BIOLOGICALBevacizumab
Bevacizumab is an approved drug
Sponsors
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: To investigate the safety and tolerability of azenosertib in combination with PLD, carboplatin, paclitaxel, or gemcitabine | Through study completion, an average of 1 year | Incidence and severity of adverse events (AEs) |
| Part 1: To identify the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of azenosertib in combination with PLD, carboplatin, paclitaxel, or gemcitabine | Through Cycle 1 (cycle is 28 days for PLD or paclitaxel, and 21 days for carboplatin, or gemcitabine) | Incidence and severity of dose-limiting toxicities (DLTs) |
| Part 2: To estimate the safety/tolerability of azenosertib in combination with bevacizumab | Through study completion, an average of 1 year | Incidence and severity of adverse events (AEs) Incidence of dose interruptions, reductions, and discontinuations due to treatment-related AEs |
| Part 2: To identify the recommended dose for Part 2 Dose Expansion | Through Cycle 1 (21 days) | — |
Countries
Australia, Bosnia and Herzegovina, Bulgaria, Georgia, Serbia, South Korea, United States
Contacts
CONTACTK-Group, Beta, Inc., a subsidiary of Zentalis Pharmaceuticals
Outcome results
None listed