Clinical trial NCT04158336: A Study of ZN-c3 in Participants With Solid Tumors
Official title: A Phase 1 Study of ZN-c3 as a Single Agent in Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Uterine Serous Carcinoma
Solid Tumors Harboring Biomarkers Related to DNA Damage Pathways
Lead sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2019-11-08
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: USC Cohort is Parallel Assignment and MOI Cohort is Single Group
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: Dose Escalation
timeFrame: Through completion, average of 1 year
measure: Food Effect Cohort
timeFrame: Through completion, approx 6 months
measure: Food Effect Cohort
timeFrame: Through completion, approximately 6 months
measure: Food Effect Cohort
timeFrame: Through completion approximately 6 month
measure: Food Effect Cohort
timeFrame: Through completion, approximately 6 mth
measure: Dose Expansion
timeFrame: Through completion, approximately 43 month
Secondary outcomes:
measure: Dose Escalation, Food Effect cohort & Dose Expansion
timeFrame: Through completion
measure: Food Effect Cohort
timeFrame: Through completion
measure: Dose Escalation, Food Effect cohort and Dose Expansion
timeFrame: Through completion.
measure: Dose Escalation, Food Effect cohort and Dose Expansion
timeFrame: Through completion..
measure: Dose Escalation, Food Effect cohort and Dose Expansion
timeFrame: Through completion...
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Site 0102
state: Arizona
city: Newport Beach
country: United States
facility: Site 0167
state: California
city: Chicago
country: United States
facility: Site 0171
state: Illinois
city: Detroit
country: United States
facility: Site 0101
state: Michigan
city: New York
country: United States
facility: Site 0173
state: New York
city: Pittsburgh
country: United States
facility: Site 0179
state: Pennsylvania
city: Houston
country: United States
facility: Site 0103
state: Texas
city: San Antonio
country: United States
facility: Site 0100
state: Texas
Study officials:
affiliation: K-Group Beta, a Zentalis Company
name: Philippe Pultar, MD
role: STUDY_DIRECTOR
References: