A Study of ZN-c3 in Women With Recurrent or Persistent Uterine Serous Carcinoma

Study Overview
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Brief Summary
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This is a Phase 2 study to evaluate the clinical activity and safety of ZN-c3 (azenosertib) in adult women with recurrent or persistent uterine serous carcinoma (USC).

Detailed Description
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This is a Phase 2 open-label, multicenter study to evaluate the clinical activity and safety of ZN-c3 (also known as azenosertib; KP-2638) in adult women with recurrent or persistent uterine serous carcinoma (USC).

Official Title
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A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN-c3 in Adult Women With Recurrent or Persistent Uterine Serous Carcinoma

Conditions
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Uterine Serous Carcinoma

Intervention / Treatment
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* Drug: ZN-c3


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Females ≥18 years of age at the time of informed consent. Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject. Subjects with endometrial carcinoma of mixed histology where the serous component comprises at least 5% of the tumor will be considered eligible. Subjects with carcinosarcomas (even if there is a serous component) are not eligible. Measurable disease per RECIST Guideline Version 1.1 Required prior therapy for endometrial cancer: Treatment with a platinum-based chemotherapy regimen. Treatment with a PD-(L)1 inhibitor Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible. 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 chemotherapy or targeted tumor therapy within 14 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). Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor for USC. A serious illness or medical condition(s) including, but not limited to: Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Experimental: ZN-c3 Single Agent<br>ZN-c3 (azenosertib) taken orally with food | Drug: ZN-c3<br>* ZN-c3 is an investigational drug.<br>* Other names: KP-2638;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of TEAEs and incidence of dose modifications | To determine the safety and tolerability of ZN-c3 in subjects with recurrent or persistent USC. | 2 years | 
| Objective Response Rate as defined by the revised RECIST v1.1 as assessed by ICR | To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator. | To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules | 2 years | 
| Duration of Response as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator. | To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules | 2 years | 
| Progression Free Survival as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator. | To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules | 2 years | 
| Clinical Benefit Rate as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator. | To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules | 2 years | 
| Time To Response as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator. | To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uterus, uterine, endometrial, endometrium, serous carcinoma, wee1, Wee-1, usc, Uterine Serous Carcinoma, serous