A Study of Azenosertib (ZN-c3) Versus Investigator's Choice Chemotherapy in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression

NCT07546500 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: ZN-c3-020GOG-3147ENGOT-ov109
• Study Type: interventional
• Target: 420
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, Phase 3 trial designed to evaluate the efficacy and safety of azenosertib compared to Investigator's choice of chemotherapy in subjects with platinum-resistant ovarian cancer whose tumors are positive for cyclin E1 protein expression.

Conditions

Ovarian Cancer

Keywords

Platinum-Resistant Ovarian Cancer (PROC); OvCa

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) per RECIST v1.1 as assessed by Investigator

  Time from randomization to the first documented tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.

  Up to approximately 24 months from the enrollment of the last subject

Secondary Outcomes (7)

• Overall survival

  Up to approximately 24 months from the enrollment of the last subject

• PFS per RECIST 1.1 as assessed by blinded independent central review (ICR)

  Up to approximately 24 months from the enrollment of the last subject

• Objective Response Rate (ORR) per RECIST v1.1 and assessed by Investigator

  Up to approximately 24 months from the enrollment of the last subject

• Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire score (EORTC QLQ)-Core 30 (C30) at each post baseline visit

  Up to approximately 24 months from the enrollment of the last subject

• Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire score (EORTC QLQ)-OV28 at each post baseline visit

  Up to approximately 24 months from the enrollment of the last subject

Study Arms (2)

Arm A Azenosertib 400 mg administered on a 5 days on, 2 days off intermittent schedule

EXPERIMENTAL

Drug: Azenosertib

Experimental: Arm C Investigator's choice of chemotherapy at the dose defined by the protocol

ACTIVE COMPARATOR

Drug: Investigator's choice of Chemotherapy

Interventions

Investigator's choice of Chemotherapy DRUG

The investigator will select the chemotherapy in accordance with the protocol defined requirements. The possible choices as defined by the protocol: * Paclitaxel * Gemcitabine * Pegylated liposomal doxorubicin (PLD) * Topotecan The selected chemotherapy will be administered intravenously

Experimental: Arm C Investigator's choice of chemotherapy at the dose defined by the protocol

Azenosertib DRUG

Azenosertib 400 mg will be administered orally.

Also known as: ZN-c3

Arm A Azenosertib 400 mg administered on a 5 days on, 2 days off intermittent schedule

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female age ≥ 18 years
• High-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer
• Measurable disease per RECIST Version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
• The subject's tumor tissue must be positive for cyclin E1 protein expression per the Sponsor's clinically validated cyclin E1 IHC investigational, in vitro diagnostic assay
• Prior Therapy:
• Subject must have platinum-resistant disease
• One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
• 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
• Adequate hematologic and organ function during the screening period

You may not qualify if:

• History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease-free. Exceptions include appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, Stage 1 uterine cancer, or other malignancies with an expected curative outcome.
• Subjects with primary platinum-refractory disease.
• Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or (PKMYT1) inhibitor for PROC.
• A serious illness or medical condition(s) including, but not limited to, the following:
• Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible.
• Acute kidney injury requiring intervention, or presence of indwelling urinary catheter or percutaneous nephrostomy.
• Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for IV alimentation, active peptic ulcer, chronic diarrhea or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption.
• Any evidence of small bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for small bowel obstruction within 3 months before randomization, or recurrent paracentesis or thoracentesis within 6 weeks before randomization.
• Active, uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral) must have completed such treatment and the infection must be considered controlled/resolved (and afebrile) by the Investigator for at least 7 days before randomization
• Myocardial impairment of any cause resulting in heart failure by New York Heart Association criteria (Class II, III or IV).
• Medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results
• Any of the following treatment interventions within the specified time frame before randomization:
• Hospitalization within 14 days
• Major surgery within 28 days
• Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter)

Sponsors & Collaborators

• K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc: lead
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator
• GOG Foundation: collaborator

MeSH Terms

Conditions

Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Central Study Contacts

Project Director

CONTACT

858.263.4333; medicalaffairs@zentalis.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 22, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): April 30, 2030
• Last Updated: April 22, 2026

Record last verified: 2026-04