A Study of Azenosertib (ZN-c3) in Participants With Solid Tumors

March 16, 2026 updated by: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

A Phase 1 Study of ZN-c3 as a Single Agent in Subjects With Solid Tumors

This is a Phase 1 open-label, multicenter study of ZN-c3 (also known as Azenosertib) monotherapy which consists of Dose Escalation, a Food Effect Cohort, and Dose Expansion.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will evaluate the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics of ZN-c3.

In Dose Escalation, the study will identify the Maximum Tolerated Dose (MTD) of ZN-c3 monotherapy in solid tumors.

The Food Effect cohort sub-study will examine ZN-c3 PK after a single dose and determine the bioavailability of ZN-c3 under fed and fasted conditions.

In Dose Expansion, single agent ZN-c3 will be evaluated at the RP2D in subjects with recurrent or persistent uterine serous carcinoma (USC) or subjects with locally advanced or metastatic solid tumor malignancies harboring biomarkers related to deoxyribonucleic acid (DNA) damage pathways.

Study Type

Interventional

Enrollment (Actual)

274

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Site 0102
    • California
      • Newport Beach, California, United States, 92663
        • Site 0167
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Site 0171
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Site 0101
    • New York
      • New York, New York, United States, 10029
        • Site 0173
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Site 0179
    • Texas
      • Houston, Texas, United States, 77030
        • Site 0103
      • San Antonio, Texas, United States, 78229
        • Site 0100

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Major Eligibility Criteria:

  1. Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
  2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  3. Adequate hematologic and organ function.
  4. Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception and for 6 months and 90 days, respectively, after the last dose of ZN-c3.

Dose Escalation Inclusion Criteria:

  1. Subjects must have a solid tumor with advanced or metastatic disease, refractory to standard therapy or for whom no standard therapy is available, or the subject is ineligible for standard therapy(ies).
  2. Measurable or evaluable disease per RECIST version 1.1.

Food Effect Cohort Inclusion Criteria:

  1. Subjects with solid tumors with advanced or metastatic disease who are refractory or ineligible to standard therapy(ies) or for whom no standard therapy is available.
  2. Subjects must have no relevant dietary restrictions, and be willing to consume a high-calorie, high-fat breakfast and other standard meals provided during the study.

Dose Expansion Inclusion Criteria:

  1. Measurable disease, defined as at least one lesion that can be accurately measured per RECIST version 1.1 criteria.
  2. Recurrent or persistent USC or locally advanced or metastatic malignancy with one or more relevant biomarkers related to deoxyribonucleic acid (DNA) damage pathways.

Major Exclusion Criteria:

  1. Prior therapy with ZN-c3 or known hypersensitivity to any drugs similar to ZN-c3 in class or any inactive ingredients present in ZN-c3.
  2. Prior therapy with a WEE1 inhibitor.
  3. A serious illness or medical condition(s).
  4. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation).
  5. Pregnant or lactating females (including the cessation of lactation) or females of childbearing potential who have a positive serum pregnancy test within 14 days prior to C1D1.
  6. Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
  7. 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of >480 ms, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid.
  8. History or current evidence of congenital or family history of long QT syndrome or Torsade de Pointes (TdP).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Agent Dose Escalation
Subjects with solid tumors with advanced or metastatic disease who are refractory or ineligible to standard therapy(ies) or for whom no standard therapy is available.
Drug: Azenosertib
Azenosertib (ZN-c3) is a study drug
Other Names:
  • ZN-c3
Experimental: Single Agent Food Effect Cohort
Subjects with solid tumors with advanced or metastatic disease who are refractory or ineligible to standard therapy(ies) or for whom no standard therapy is available. This cohort will give subjects the option to continue treatment after PK assessments are completed.
Drug: Azenosertib
Azenosertib (ZN-c3) is a study drug
Other Names:
  • ZN-c3
Experimental: Single Agent Dose Expansion
Subjects with recurrent, platinum-resistant HGSOC; histologically confirmed USC; or either CCNE1-amplified/cyclinE1-positive solid tumors; or subjects who roll over from ZN-c3 pharmacology studies.
Drug: Azenosertib
Azenosertib (ZN-c3) is a study drug
Other Names:
  • ZN-c3

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation
Time Frame: Through completion, average of 1 year
To investigate the safety and tolerability of single agent ZN-c3, including identification of the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D), based on the incidence and severity of adverse events (AEs) and dose-limiting toxicities (DLTs) in DLT-evaluable subjects.
Through completion, average of 1 year
Food Effect Cohort
Time Frame: Through completion, approx 6 months
To characterize and compare the PK (Cmax.) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
Through completion, approx 6 months
Food Effect Cohort
Time Frame: Through completion, approximately 6 months
To characterize and compare the PK (Tmax) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
Through completion, approximately 6 months
Food Effect Cohort
Time Frame: Through completion approximately 6 month
To characterize and compare the PK (AUC0-last,AUC0-∞) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
Through completion approximately 6 month
Food Effect Cohort
Time Frame: Through completion, approximately 6 mth
To characterize and compare the PK (T1/2) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
Through completion, approximately 6 mth
Dose Expansion
Time Frame: Through completion, approximately 43 month
To investigate the clinical activity of WEE1 inhibition based on the objective response rate (ORR) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Through completion, approximately 43 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation, Food Effect cohort & Dose Expansion
Time Frame: Through completion
To obtain preliminary estimates of antitumor efficacy of single agent ZN-c3 based on objective response rate (ORR) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Through completion
Food Effect Cohort
Time Frame: Through completion
To investigate electrocardiogram intervals (QTc Interval) via Holter monitoring after a single dose of ZN-c3 under fed and fasting conditions.
Through completion
Dose Escalation, Food Effect cohort and Dose Expansion
Time Frame: Through completion.
To obtain preliminary estimates of antitumor efficacy of single agent ZN-c3 based on Duration of Response (DOR) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Through completion.
Dose Escalation, Food Effect cohort and Dose Expansion
Time Frame: Through completion..
To obtain preliminary estimates of antitumor efficacy of single agent ZN-c3 based on Progression Free Survival (PFS) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Through completion..
Dose Escalation, Food Effect cohort and Dose Expansion
Time Frame: Through completion...
To obtain preliminary estimates of antitumor efficacy of single agent ZN-c3 based on Clinical Benefit Rate (CBR) defined as complete response, partial response or stable disease according to the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Through completion...

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Investigators

  • Study Director: Philippe Pultar, MD, K-Group Beta, a Zentalis Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2019

Primary Completion (Actual)

May 6, 2025

Study Completion (Actual)

May 6, 2025

Study Registration Dates

First Submitted

November 4, 2019

First Submitted That Met QC Criteria

November 6, 2019

First Posted (Actual)

November 8, 2019

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZN-c3-001

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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