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

NCT04158336 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ZN-c3-001
• Study Type: interventional
• Target: 274
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Solid Tumor

Keywords

Solid Tumors Harboring Biomarkers Related to DNA Damage Pathways

Outcome Measures

Primary Outcomes (6)

• 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.

  Through completion, average of 1 year

• 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.

  Through completion, approx 6 months

• 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.

  Through completion, approximately 6 months

• 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.

  Through completion approximately 6 month

• 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.

  Through completion, approximately 6 mth

• 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

  Through completion, approximately 43 month

Secondary Outcomes (5)

• Dose Escalation, Food Effect cohort & Dose Expansion

  Through completion

• Food Effect Cohort

  Through completion

• Dose Escalation, Food Effect cohort and Dose Expansion

  Through completion.

• Dose Escalation, Food Effect cohort and Dose Expansion

  Through completion..

• Dose Escalation, Food Effect cohort and Dose Expansion

  Through completion...

Study Arms (3)

Single Agent Dose Escalation

EXPERIMENTAL

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

Single Agent Food Effect Cohort

EXPERIMENTAL

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

Single Agent Dose Expansion

EXPERIMENTAL

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

Azenosertib DRUG

Azenosertib (ZN-c3) is a study drug

Also known as: ZN-c3

Single Agent Dose Escalation; Single Agent Dose Expansion; Single Agent Food Effect Cohort

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.
• Prior therapy with a WEE1 inhibitor.
• A serious illness or medical condition(s).
• Unresolved toxicity of Grade \>1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation).
• 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.
• Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
• 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.
• History or current evidence of congenital or family history of long QT syndrome or Torsade de Pointes (TdP).

Sponsors & Collaborators

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

Study Sites (8)

Site 0102

Tucson, Arizona, 85719, United States

Location

Site 0167

Newport Beach, California, 92663, United States

Location

Site 0171

Chicago, Illinois, 60637, United States

Location

Site 0101

Detroit, Michigan, 48201, United States

Location

Site 0173

New York, New York, 10029, United States

Location

Site 0179

Pittsburgh, Pennsylvania, 15213, United States

Location

Site 0103

Houston, Texas, 77030, United States

Location

Site 0100

San Antonio, Texas, 78229, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: USC Cohort is Parallel Assignment and MOI Cohort is Single Group

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 8, 2019
• Study Start: November 1, 2019
• Primary Completion: May 6, 2025
• Study Completion: May 6, 2025
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)