A Study of ZN-c3 in Participants With Solid Tumors

• ClinicalTrials.gov Identifier: NCT04158336
• Recruitment Status: Recruiting
• First Posted: November 8, 2019
• Last Update Posted: February 1, 2023
• Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
• Information provided by (Responsible Party): K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: ZN-c3	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 146 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: USC Cohort is Parallel Assignment and MOI Cohort is Single Group
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of ZN-c3 as a Single Agent in Subjects With Solid Tumors
• Actual Study Start Date: November 1, 2019
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: August 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single Agent Dose Escalation; 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.	Drug: ZN-c3; ZN-c3 is a study drug; Other Name: Study Drug
Experimental: Single Agent Food Effect Cohort; 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.	Drug: ZN-c3; ZN-c3 is a study drug; Other Name: Study Drug
Experimental: Single Agent Dose Expansion; 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.	Drug: ZN-c3; ZN-c3 is a study drug; Other Name: Study Drug

Outcome Measures

Primary Outcome Measures :

1. Dose Escalation [ Time Frame: 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.
2. Food Effect Cohort [ Time Frame: Through completion, approx 6 months ]
   To characterize and compare the PK (Cmax.) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
3. Food Effect Cohort [ Time Frame: Through completion, approximately 6 months ]
   To characterize and compare the PK (Tmax) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
4. Food Effect Cohort [ Time Frame: Through completion approximately 6 month ]
   To characterize and compare the PK (AUC0-last,AUC0-∞) of ZN-c3 following a single dose of ZN-c3 under fed and fasting conditions.
5. Food Effect Cohort [ Time Frame: 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.
6. Dose Expansion [ Time Frame: 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

Secondary Outcome Measures :

1. Dose Escalation, Food Effect cohort & Dose Expansion [ Time Frame: 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.
2. Food Effect Cohort [ Time Frame: Through completion ]
   To investigate electrocardiogram intervals (QTc Interval) via Holter monitoring after a single dose of ZN-c3 under fed and fasting conditions.
3. Dose Escalation, Food Effect cohort and Dose Expansion [ Time Frame: Through completion. ]
   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.
4. Dose Escalation, Food Effect cohort and Dose Expansion [ Time Frame: Through completion.. ]
   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.
5. Dose Escalation, Food Effect cohort and Dose Expansion [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Contacts

Contact: Project Director; 858-263-4333; medicalaffairs@zentalis.com

Locations

United States, Arizona

Site 0102; Recruiting

Tucson, Arizona, United States, 85719

United States, California

Site 0167; Recruiting

Newport Beach, California, United States, 92663

United States, Illinois

Site 0171; Recruiting

Chicago, Illinois, United States, 60637

United States, Michigan

Site 0101; Recruiting

Detroit, Michigan, United States, 48201

United States, New York

Site 0173; Recruiting

New York, New York, United States, 10029

United States, Pennsylvania

Site 0179; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

United States, Texas

Site 0103; Recruiting

Houston, Texas, United States, 77030

Site 0100; Recruiting

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

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

Investigators

• Study Director: Philippe Pultar, MD; K-Group Beta, a Zentalis Company

More Information

• Responsible Party: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT04158336
• Other Study ID Numbers: ZN-c3-001
• First Posted: November 8, 2019
• Last Update Posted: February 1, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc:

Uterine Serous Carcinoma; Solid Tumors Harboring Biomarkers Related to DNA Damage Pathways

Additional relevant MeSH terms:

Neoplasms