A Study of ZN-c3 in Participants With Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase 1 Study of ZN-c3 as a Single Agent in Subjects With Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04158336
• Other study ID #: ZN-c3-001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 1, 2019
• Est. completion date: August 2023

Study information

• Verified date: January 2023
• Source: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
• Contact: Project Director
• Phone: 858-263-4333
• Email: medicalaffairs[@]zentalis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 146
• Est. completion date: August 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Major Eligibility Criteria:

1. Age = 18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.

2. Eastern Cooperative Oncology Group (ECOG) performance status =2.

3. Adequate hematologic and organ function.

4. Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception and for 6 months and 90 days, respectively, after the last dose of ZN-c3.

Dose Escalation 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 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).

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• ZN-c3
ZN-c3 is a study drug

Locations

Country	Name	City	State
United States	Site 0171	Chicago	Illinois
United States	Site 0101	Detroit	Michigan
United States	Site 0103	Houston	Texas
United States	Site 0173	New York	New York
United States	Site 0167	Newport Beach	California
United States	Site 0179	Pittsburgh	Pennsylvania
United States	Site 0100	San Antonio	Texas
United States	Site 0102	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Food Effect Cohort	To characterize and compare the PK (AUC0-last,AUC0-8) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.	Through completion approximately 6 month
Primary	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
Primary	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	Dose Escalation, Food Effect cohort & Dose Expansion	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.	Through completion
Secondary	Food Effect Cohort	To investigate electrocardiogram intervals (QTc Interval) via Holter monitoring after a single dose of ZN-c3 under fed and fasting conditions.	Through completion
Secondary	Dose Escalation, Food Effect cohort and Dose Expansion	To obtain preliminary estimates of antitumor efficacy of single agent ZN-c3 based on Duration of Response (DOR) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Through completion.
Secondary	Dose Escalation, Food Effect cohort and Dose Expansion	To obtain preliminary estimates of antitumor efficacy of single agent ZN-c3 based on Progression Free Survival (PFS) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Through completion..
Secondary	Dose Escalation, Food Effect cohort and Dose Expansion	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.	Through completion...