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

Phase 1

Active, not recruiting

• Conditions: Osteosarcoma
• Interventions: Drug: ZN-c3; Drug: Gemcitabine

• Registration Number: NCT04833582
• Lead Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Brief Summary

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

Detailed Description

This is a phase 1/2 dose escalation and dose expansion study, evaluating the clinical activity and safety, pharmacodynamics, and pharmacokinetics of ZN-c3 in combination with gemcitabine in relapsed or refractory osteosarcoma.

Study Timeline

• Study First Submitted: 2021-03-25
• Study First Submitted QC: 2021-04-02
• Study First Posted: 2021-04-06
• Study Start: 2021-08-01
• Primary Completion: 2023-08-30
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-10
• Last Update Posted: 2023-11-14
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 12-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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Combination ZN-c3 with Gemcitabine	ZN-c3	-
Combination ZN-c3 with Gemcitabine	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
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.	During phase 2, at 18 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Event-free survival (EFS) per RECIST Guideline version 1.1.	At 12 months	EFS is defined as time from study enrollment until date of last contact, date of disease progression, or detection of disease at a previously uninvolved site, or date of death.
Terminal half-life of the plasma PK concentration.	Through completion, approximately 42 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 PK time to maximum concentration (Tmax).	Through completion, approximately 42 months
Plasma pharmacokinetics (PK) maximum concentration (Cmax).	Through completion, approximately 42 months
Area under the plasma concentration versus timepoint curve (AUC last).	Through completion, approximately 42 months
Median overall survival (OS) and OS at 12 months per RECIST Guideline version 1.1.	At 12 months	OS is defined as the time from date of first dosing until the date of death.

Trial Locations

Locations (17)

Site 3604; 🇫🇷 Bordeaux, France

Site 3606; 🇫🇷 Paris, France

Site 0106; 🇺🇸 Los Angeles, California, United States

Site 0124; 🇺🇸 Oakland, California, United States

Site 0107; 🇺🇸 Cincinnati, Ohio, United States

Site 0103; 🇺🇸 Houston, Texas, United States

Site 0122; 🇺🇸 Seattle, Washington, United States

Site 0197; 🇺🇸 Nashville, Tennessee, United States

Site 3605; 🇫🇷 Toulouse, France

Site 0105; 🇺🇸 New York, New York, United States

Site 0195; 🇺🇸 Santa Monica, California, United States

Site 0193; 🇺🇸 Memphis, Tennessee, United States

Site 0188; 🇺🇸 Richmond, Virginia, United States

Site 3601; 🇫🇷 Lyon, France

Site 3602; 🇫🇷 Marseille, France

Site 0123; 🇺🇸 Portland, Oregon, United States

University of Florida College of Medicine; 🇺🇸 Gainesville, Florida, United States