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CompletedNCT04158336Updated Mar 18, 2026

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

A Phase 1 interventional study of Azenosertib in Solid Tumor, sponsored by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. Completed at 8 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-18.

Sponsored by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
274
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Solid Tumor

Keywords

  • Solid Tumors Harboring Biomarkers Related to DNA Damage Pathways
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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).
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
274 participants (actual)

Study arms

  • 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

  • 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

  • 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

Interventions

  • DrugAzenosertib

    Azenosertib (ZN-c3) is a study drug

    Also known as: ZN-c3

05

What researchers measure

Primary outcomes

  1. Dose Escalation

    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.

    Time frame: Through completion, average of 1 year

  2. Food Effect Cohort

    To characterize and compare the PK (Cmax.) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.

    Time frame: Through completion, approx 6 months

  3. Food Effect Cohort

    To characterize and compare the PK (Tmax) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.

    Time frame: Through completion, approximately 6 months

  4. Food Effect Cohort

    To characterize and compare the PK (AUC0-last,AUC0-∞) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.

    Time frame: Through completion approximately 6 month

  5. Food Effect Cohort

    To characterize and compare the PK (T1/2) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.

    Time frame: Through completion, approximately 6 mth

  6. Dose Expansion

    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

    Time frame: Through completion, approximately 43 month

Secondary outcomes

  1. Dose Escalation, Food Effect cohort & Dose Expansion

    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.

    Time frame: Through completion

  2. Food Effect Cohort

    To investigate electrocardiogram intervals (QTc Interval) via Holter monitoring after a single dose of ZN-c3 under fed and fasting conditions.

    Time frame: Through completion

  3. Dose Escalation, Food Effect cohort and Dose Expansion

    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.

    Time frame: Through completion.

  4. Dose Escalation, Food Effect cohort and Dose Expansion

    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.

    Time frame: Through completion..

  5. Dose Escalation, Food Effect cohort and Dose Expansion

    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.

    Time frame: Through completion...

06

Study locations

8 sites
  • Site 0102
    Tucson, Arizona 85719, United States
  • Site 0167
    Newport Beach, California 92663, United States
  • Site 0171
    Chicago, Illinois 60637, United States
  • Site 0101
    Detroit, Michigan 48201, United States
  • Site 0173
    New York, New York 10029, United States
  • Site 0179
    Pittsburgh, Pennsylvania 15213, United States
  • Site 0103
    Houston, Texas 77030, United States
  • Site 0100
    San Antonio, Texas 78229, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT04158336
Lead sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Responsible party
Sponsor
First posted
Nov 8, 2019
Start date
Nov 1, 2019
Primary completion
May 6, 2025
Completion
May 6, 2025
Last update
Mar 18, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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