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)
Overview
- Phase
- Phase 2
- Intervention
- azenosertib
- Conditions
- High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer
- Sponsor
- K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
- Enrollment
- 310
- Locations
- 168
- Primary Endpoint
- Objective Response Rate (ORR) defined by RECIST v1.1 [Part 2]
- Status
- Recruiting
- Last Updated
- yesterday
Overview
Brief Summary
This is a multi-part Phase 2 study to evaluate the efficacy and safety of azenosertib (ZN-c3) in subjects with Platinum-Resistant, High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Part 2 of the study will be conducted in subjects whose tumors are Cyclin E1 positive as determined by central review using the Sponsor's investigational clinical trial assay.
Detailed Description
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years
- •High-grade serous ovarian, fallopian tube or primary peritoneal cancer
- •Tumor testing (archival acceptable) confirms a positive Cyclin E1 protein status result determined by IHC using the Sponsor's investigational clinical trial assay
- •Prior therapy:
- •Subjects must have platinum-resistant disease
- •Parts 2a and 2b: One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
- •Part 2c: Subjects with PROC may have 1 to 4 prior lines or regimens. Prior treatment in this cohort includes a weekly taxane regimen, either as single agent or in combination, per protocol
- •Prior bevacizumab treatment is required, if eligible per standard of care
- •Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
- •Prior mirvetuximab treatment is required, if eligible per standard of care
Exclusion Criteria
- •Primary platinum-refractory disease
- •Subjects with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, low-grade, borderline, or other ovarian tumors
- •Any of the following treatment interventions within the specified time frame prior to C1D1:
- •Major surgery within 28 days
- •Hospitalization within 14 days
- •Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter);
- •Radiation therapy within 21 days;
- •Autologous or allogeneic stem cell transplant within 3 months.
- •Current use of any other investigational drug therapy \<28 days or 5 half-lives (whichever is shorter).
- •Inability to discontinue treatment prescription or non-prescription drugs, or to discontinue consumption of food and herbal supplements that are strong or moderate CYP3A inhibitors and inducers or P-gp inhibitors at least 14 days prior to C1D
Arms & Interventions
Part 1a/1b (Completed Enrollment)
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule.
Intervention: azenosertib
Part 2b
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule
Intervention: azenosertib
Part 2a: Arm 1 (Completed Enrollment)
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule
Intervention: azenosertib
Part 2a: Arm 2 (Completed Enrollment)
Azenosertib 300mg administered once daily on a 5 days on, 2 days off intermittent schedule
Intervention: azenosertib
Part 2c
Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule
Intervention: azenosertib
Outcomes
Primary Outcomes
Objective Response Rate (ORR) defined by RECIST v1.1 [Part 2]
Time Frame: Up to approximately 12 months from the enrollment of the last subject
Participants who achieve partial response (PR) or complete response (CR) per RECIST v1.1 criteria.
Secondary Outcomes
- Duration of response (DOR) defined by RECIST v1.1 [Part 2](Up to approximately 12 months from the enrollment of the last subject)
- Progression free survival (PFS) defined by RECIST v1.1 [Part 2](Up to approximately 12 months from the enrollment of the last subject)
- Clinical Benefit Rate (CBR) defined by RECIST v1.1 [Part 2](Up to approximately 12 months from the enrollment of the last subject)
- CA-125 response by GCIG criteria [Part 2](Up to approximately 12 months from the enrollment of the last subject)
- Number of Subjects experiencing treatment emergent adverse events (TEAEs) [Part 2](Up to approximately 12 months from the enrollment of the last subject)