A Study of ZN-c3 in Participants With Solid Tumors

Phase 1

Recruiting

• Conditions: Solid Tumor
• Interventions: Drug: ZN-c3

• Registration Number: NCT04158336
• Lead Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Brief Summary

This is a Phase 1 open-label, multicenter study of ZN-c3 monotherapy which consists of Dose Escalation, a Food Effect Cohort, and Dose Expansion.

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.

Study Timeline

• Study Start: 2019-11-01
• Study First Submitted: 2019-11-04
• Study First Submitted QC: 2019-11-06
• Study First Posted: 2019-11-08
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-30
• Last Update Posted: 2023-02-01
• Primary Completion: 2023-05
• Study Completion: 2023-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 146

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

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single Agent Food Effect Cohort	ZN-c3	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.
Single Agent Dose Expansion	ZN-c3	Subjects with histologically confirmed recurrent or persistent USC who have had treatment with at least 1 prior platinum-based chemotherapy regimen for management of advanced or metastatic USC and subjects with locally advanced or metastatic malignancy with one or more relevant biomarkers related to DNA damage pathways.
Single Agent Dose Escalation	ZN-c3	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.

Primary Outcome Measures

Name	Time	Method
Food Effect Cohort	Through completion, approximately 6 mth	To characterize and compare the PK (T1/2) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
Dose Expansion	Through completion, approximately 43 month	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
Dose Escalation	Through completion, average of 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Food Effect Cohort	Through completion	To investigate electrocardiogram intervals (QTc Interval) via Holter monitoring after a single dose of ZN-c3 under fed and fasting conditions.
Dose Escalation, Food Effect cohort and Dose Expansion	Through completion...	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.
Dose Escalation, Food Effect cohort & Dose Expansion	Through completion	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.

Trial Locations

Locations (8)

Site 0102; 🇺🇸 Tucson, Arizona, United States

Site 0103; 🇺🇸 Houston, Texas, United States

Site 0179; 🇺🇸 Pittsburgh, Pennsylvania, United States

Site 0171; 🇺🇸 Chicago, Illinois, United States

Site 0101; 🇺🇸 Detroit, Michigan, United States

Site 0173; 🇺🇸 New York, New York, United States

Site 0167; 🇺🇸 Newport Beach, California, United States

Site 0100; 🇺🇸 San Antonio, Texas, United States