A Study of ZN-c3 in Subjects With High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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This is a Phase 2 open-label, multicenter study to evaluate the clinical activity, safety, pharmacokinetics (PK), and biomarker profile of ZN-c3 in subjects with High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer

Official Title
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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 (ZN-c3-005/GOG-3066/DENALI)

Conditions
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High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Intervention / Treatment
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* Drug: ZN-c3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years at the time of informed consent. Histologically or cytologically confirmed recurrent, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer Prior therapy: Subjects must have platinum-resistant disease Documented progressive disease ≤6 months One to 4 prior lines or regimens are allowed (1 to 5 in 1b) Prior bevacizumab treatment is required (except where not standard of care treatment) Subjects must have at least one measurable lesion as defined by RECIST Guideline Version 1.1. Performance Status: Eastern Cooperative Oncology Group (ECOG) score of ≤1. Adequate hematologic and organ function Exclusion Criteria: Any of the following treatment interventions within the specified time frame prior to C1D1: Major surgery within 28 days (any surgical incision should be fully healed prior to study drug administration); Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter); 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. 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/ and moderate CYP3A4 inhibitors and inducers, or P-gp inhibitors at least 14 days prior to C1D1. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation). Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open-label with ZN-c3 (also known as azenosertib)<br> | Drug: ZN-c3<br>* ZN-c3 is an investigational drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: To investigate the safety and tolerability of ZN-c3 | Frequency and severity of TEAEs according to the NCI-CTCAE Version 5.0 | Assessed from Cycle 1 Day 1 until 30 days after treatment discontinuation, up to 50 months (each cycle is 21 days) | 
| Part 2: To investigate the antitumor activity of ZN-c3 based on the Objective Response Rate (ORR) | ORR is defined by RECIST v1.1 | Assessed every 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: 1) To investigate the antitumor activity of ZN-c3 | Objective Response Rate (ORR) as defined by RECIST v1.1 | Assessed every 6 weeks up to 50 months | 
| Part 1: 2) To investigate the antitumor activity of ZN-c3 | Overall Survival (OS) | Assessed on treatment and then every 3 months up to 50 months | 
| Part 1: 3) To investigate the plasma PK of ZN-c3 | The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined | Assessed on Cycle 1 Day 15 and all subsequent Day 1 up to Cycle 6 (each cycle is 21 days) | 
| Part 1: 4) To investigate the plasma PK of ZN-c3 | Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) will be determined | Assessed on Cycle 1 Day 15 and all subsequent Day 1 up to Cycle 6 (each cycle is 21 days) | 
| Part 1: 4) To investigate the plasma PK of ZN-c3 | The Time to maximum plasma concentration (Tmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined | Assessed on Cycle 1 Day 15 and all subsequent Day 1 up to Cycle 6 (each cycle is 21 days) | 
| Part 2: 1) To further investigate the antitumor activity of ZN-c3 | Objective Response Rate (ORR) as defined by RECIST v1.1 | Assessed every 6 weeks up to 50 months | 
| Part 2: 2) To further investigate the antitumor activity of ZN-c3 | Overall survival (OS) | Assessed on treatment and then every 3 months up to 50 months | 
| Part 2: 3) To investigate the safety and tolerability of ZN-c3 | Frequency and severity of TEAEs graded according to the NCI-CTCAE Version 5.0 | Assessed from Cycle 1 Day 1 until 30 days after treatment discontinuation, up to 50 months (each cycle is 21 days) | 
| Part 2: 4) To investigate the plasma PK of ZN-c3 | The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined | Assessed on Cycle 1 Day 15 and all subsequent Day 1 up to Cycle 6 (each cycle is 21 days) | 
| Part 2: 5) To investigate the plasma PK of ZN-c3 | Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) will be determined | Assessed on Cycle 1 Day 15 and all subsequent Day 1 up to Cycle 6 (each cycle is 21 days) | 
| Part 2: 5) To investigate the plasma PK of ZN-c3 | The Time to maximum plasma concentration (Tmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined | Assessed on Cycle 1 Day 15 and all subsequent Day 1 up to Cycle 6 (each cycle is 21 days) |