A Study of Azenosertib (ZN-c3) in Patients With Ovarian Cancer (MUIR)

A Phase 1b Study of ZN-c3 in Combination With Chemotherapy or Bevacizumab in Subjects With Ovarian, Peritoneal, or Fallopian Tube Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Fallopian Tube Cancer; Solid Tumor; Epithelial Ovarian Cancer; Peritoneal Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Carboplatin; Drug: Pegylated liposomal doxorubicin; Drug: Paclitaxel; Drug: Azenosertib; Biological: Bevacizumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 172
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: K-Group, Beta, Inc., a subsidiary of Zentalis Pharmaceuticals; Phone Number: 8582634333; Email: medicalaffairs@zentalis.com

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Completed
      • Site 2707
    • Sunshine Coast, Queensland, Australia, 4556
      • Completed
      • Site 2708
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Completed
      • Site 2709
  • Victoria
    • Melbourne, Victoria, Australia, 3144
      • Recruiting
      • Site 2706
    • Melbourne, Victoria, Australia, 3121
      • Recruiting
      • Site 2716
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Site 2705
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • Completed
    • Site 1001
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Completed
    • Site 1002
  • Tuzla, Bosnia and Herzegovina, 75000
    • Completed
    • Site 1003
• Bulgaria
  • Panagyurishte, Bulgaria, 4500
    • Completed
    • Site 1202
  • Sofia, Bulgaria, 1632
    • Completed
    • Site 1201
• Georgia
  • Tbilisi, Georgia, 0112
    • Completed
    • Site 1401
• Serbia
  • Belgrade, Serbia, 11080
    • Completed
    • Site 1902
• South Korea
  • Busan, South Korea
    • Completed
    • Site 2901
  • Seoul, South Korea, 03080
    • Completed
    • Site 2903
  • Seoul, South Korea, 05505
    • Completed
    • Site 2904
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Site 0264
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Site 0104
  • Missouri
    • St Louis, Missouri, United States, 53110
      • Recruiting
      • Site 0111
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Site 0173
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Site 0259
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Recruiting
      • Site 0191
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Completed
      • Site 0196
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Site 0103

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Azenosertib + carboplatin; Azenosertib in combination with carboplatin	Drug: Carboplatin; Carboplatin is an approved drug; Drug: Azenosertib; Investigational drug; Other Names: ZN-c3
Experimental: Part 1: Azenosertib + PLD; Azenosertib in combination with pegylated liposomal doxorubicin (PLD)	Drug: Pegylated liposomal doxorubicin; Pegylated liposomal doxorubicin (PLD) is an approved drug; Drug: Azenosertib; Investigational drug; Other Names: ZN-c3
Experimental: Part 1: Azenosertib + paclitaxel; Azenosertib in combination with paclitaxel	Drug: Paclitaxel; Paclitaxel is an approved drug; Drug: Azenosertib; Investigational drug; Other Names: ZN-c3
Experimental: Part 1: Azenosertib + gemcitabine; Azenosertib in combination with gemcitabine	Drug: Gemcitabine; Gemcitabine is an approved drug; Drug: Azenosertib; Investigational drug; Other Names: ZN-c3
Experimental: Part 2: Azenosertib + bevacizumab; Azenosertib in combination with bevacizumab	Drug: Azenosertib; Investigational drug; Other Names: ZN-c3; Biological: Bevacizumab; Bevacizumab is an approved drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: To investigate the safety and tolerability of azenosertib in combination with PLD, carboplatin, paclitaxel, or gemcitabine	Incidence and severity of adverse events (AEs)	Through study completion, an average of 1 year
Part 1: To identify the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of azenosertib in combination with PLD, carboplatin, paclitaxel, or gemcitabine	Incidence and severity of dose-limiting toxicities (DLTs)	Through Cycle 1 (cycle is 28 days for PLD or paclitaxel, and 21 days for carboplatin, or gemcitabine)
Part 2: To estimate the safety/tolerability of azenosertib in combination with bevacizumab	Incidence and severity of adverse events (AEs) Incidence of dose interruptions, reductions, and discontinuations due to treatment-related AEs	Through study completion, an average of 1 year
Part 2: To identify the recommended dose for Part 2 Dose Expansion		Through Cycle 1 (21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To obtain estimates of clinical activity by determining the objective response rate (ORR) of ZN-c3 in combination with PLD, carboplatin, paclitaxel, or gemcitabine	Objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1	Through completion, approximately 40 months
To obtain estimates of clinical activity by determining the duration of response (DOR) of ZN-c3 in combination with PLD, carboplatin, paclitaxel, or gemcitabine	Duration of response (DOR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1	Through completion, approximately 40 months
To obtain estimates of clinical activity by determining the progression-free survival (PFS) of ZN-c3 in combination with PLD, carboplatin, paclitaxel, or gemcitabine	Progression-free survival (PFS) as defined by RECIST version 1.1 and clinical criteria	Through completion, approximately 40 months
To obtain estimates of clinical activity by determining the time to CA125 progression of ZN-c3 in combination with PLD, carboplatin, paclitaxel, or gemcitabine	Time to CA125 progression according to the Gynecologic Cancer Intergroup (GCIG) criteria	Through completion, approximately 40 months
To investigate the plasma pharmacokinetics (PK) of ZN-c3 in combination with PLD, carboplatin, paclitaxel, or gemcitabine	Plasma PK parameters of ZN-c3 (and its potential metabolites as applicable)	Through completion, approximately 40 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the PK of ZN-c3 in tumor tissue	ZN-c3 concentrations (and its potential metabolites as applicable) in tumor tissue	At Cycle 1 Day 1 and Cycle 2 Day 1 (pre-dose) (each cycle is 28 days for PLD or paclitaxel, and 21 days for carboplatin or gemcitabine)
To investigate the pharmacodynamics of ZN-c3 on the biological activity of γH2AX	Biological activity in pre- versus post-dose tumor tissue and hair follicle samples of γH2AX	Through completion, approximately 40 months
To investigate the pharmacodynamics of ZN-c3 on the biological activity of phosphorylated cyclin-dependent kinase 1 (phospho-CDK1)	Biological activity in pre- versus post-dose tumor tissue and hair follicle samples of phosphorylated cyclin-dependent kinase 1 (phospho-CDK1)	Through completion, approximately 40 months
To investigate the pharmacodynamics of ZN-c3 on the biological activity of Ki-67	Biological activity in pre- versus post-dose tumor tissue and hair follicle samples of Ki-67	Through completion, approximately 40 months
To investigate the pharmacodynamics of ZN-c3 on Baseline Cyclin E expression	Including, but not limited to, Baseline Cyclin E expression in pre-dose tumor tissue	Through completion, approximately 40 months
To investigate the pharmacodynamics of ZN-c3 on molecular determinants of sensitivity to ZN-c3	Molecular determinants of sensitivity to ZN-c3 including but not limited to Baseline DNA Damage Repair (DDR) gene mutations, deletions, copy number variations or indices of genetic instability in either tumor tissue or cell-free DNA (cfDNA)	Through completion, approximately 40 months

Collaborators and Investigators

• Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
• Investigators: Study Director: Philippe Pultar, MD, K-Group Beta

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2020
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Solid Tumor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Fallopian Tube Diseases; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Bevacizumab; Gemcitabine; Carboplatin; Paclitaxel; liposomal doxorubicin
• Other Study ID Numbers: ZN-c3-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No