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

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc31 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Osteosarcoma

Interventions

AzenosertibDRUG

Azenosertib is an investigational drug.

GemcitabineDRUG

Gemcitabine is an approved drug

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (17)

Site 0106

Los Angeles, California, United States

Site 0124

Oakland, California, United States

Site 0195

Santa Monica, California, United States

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: During phase 2, at 18 weeks

Secondary Outcomes

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

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.

Time frame: At 12 months

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

OS is defined as the time from date of first dosing until the date of death.

Time frame: 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.

Time frame: Through completion, approximately 42 months

Plasma pharmacokinetics (PK) maximum concentration (Cmax).

Time frame: Through completion, approximately 42 months

Plasma PK time to maximum concentration (Tmax).

Time frame: Through completion, approximately 42 months

Data from ClinicalTrials.gov

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