A Study of Azenosertib (ZN-c3) in Combination With Gemcitabine in Subjects With Osteosarcoma

NCT04833582 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ZN-c3-003
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 17

Brief Summary

This is a phase 1/2 study of azenosertib (ZN-c3) in combination with gemcitabine in adult and pediatric subjects with relapsed or refractory osteosarcoma.

Conditions

Osteosarcoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLT) in DLT evaluable subjects and the incidence and severity of adverse events.

  Through Cycle 1 (21 days) Phase 1

• Event-free survival (EFS) at 18 weeks per RECIST (Response Evaluation Criteria in Solid Tumors) Guideline version 1.1.

  EFS at 18 weeks is defined as time from study enrollment until date of disease progression, or detection of disease at a previously uninvolved site, or date of death of the subjects at 18 weeks.

  During phase 2, at 18 weeks

Secondary Outcomes (7)

• Event-free survival (EFS) per RECIST Guideline version 1.1.

  At 12 months

• Median overall survival (OS) and OS at 12 months per RECIST Guideline version 1.1.

  At 12 months

• The frequency and severity of adverse events (AEs) and laboratory abnormalities per the National Cancer Institute Common Terminology (NCI CTCAE) version 5.0.lities.

  Through completion, approximately 42 months

• Plasma pharmacokinetics (PK) maximum concentration (Cmax).

  Through completion, approximately 42 months

• Plasma PK time to maximum concentration (Tmax).

  Through completion, approximately 42 months

Study Arms (1)

Azenosertib in combination with Gemcitabine

EXPERIMENTAL

Azenosertib (ZN-c3) in combination with Gemcitabine

Drug: Azenosertib; Drug: Gemcitabine

Interventions

Gemcitabine DRUG

Gemcitabine is an approved drug

Also known as: Gemzar

Azenosertib in combination with Gemcitabine

Azenosertib DRUG

Azenosertib is an investigational drug.

Also known as: ZN-c3

Azenosertib in combination with Gemcitabine

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 12 years at the time of informed consent
• Bodyweight ≥ 40 kg
• Histologically documented relapsed or metastatic osteosarcoma.
• Must have measurable disease according to RECIST Guideline version 1.1 criteria.
• Adequate hematologic and organ function.
• Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception per institutional standard prior to the first dose and for 6 months after study treatment discontinuation.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Unresolved toxicity of Grade \>1 attributed to prior therapies (excluding: Grade ≤2 neuropathy, alopecia, or skin pigmentation)
• Prior therapy with a WEE1 inhibitor
• A serious illness or medical condition(s).
• Pregnant or lactating females. Females of childbearing potential with a positive serum pregnancy test \<14 days to Day 1.
• Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
• lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of \>470 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 Torsades de Pointes (TdP).
• Taking medications with a known risk of TdP.
• Administration of strong and moderate CYP3A4 inhibitors/inducers and strong and moderate P-gp inhibitors.

Sponsors & Collaborators

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

Study Sites (17)

Site 0106

Los Angeles, California, 90095, United States

Location

Site 0124

Oakland, California, 94609, United States

Location

Site 0195

Santa Monica, California, 90403, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Site 0105

New York, New York, 10065, United States

Location

Site 0107

Cincinnati, Ohio, 45229, United States

Location

Site 0123

Portland, Oregon, 97239, United States

Location

Site 0193

Memphis, Tennessee, 38105, United States

Location

Site 0197

Nashville, Tennessee, 37332, United States

Location

Site 0103

Houston, Texas, 77030, United States

Location

Site 0188

Richmond, Virginia, 23298, United States

Location

Site 0122

Seattle, Washington, 98195, United States

Location

Site 3604

Bordeaux, 33000, France

Location

Site 3601

Lyon, 69008, France

Location

Site 3602

Marseille, 13385, France

Location

Site 3606

Paris, 75248, France

Location

Site 3605

Toulouse, 31100, France

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

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

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 6, 2021
• Study Start: August 1, 2021
• Primary Completion: August 30, 2023
• Study Completion: March 30, 2024
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

US (12); FR (5)