Solid Tumor
Conditions
Keywords
Solid Tumors Harboring Biomarkers Related to DNA Damage Pathways
Brief summary
This is a Phase 1 open-label, multicenter study of ZN-c3 (also known as Azenosertib) 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.
Interventions
DRUGAzenosertib
Azenosertib (ZN-c3) is a study drug
Sponsors
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
USC Cohort is Parallel Assignment and MOI Cohort is Single Group
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Food Effect Cohort | 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. |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 Duration of Response (DOR) as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
Countries
United States
Outcome results
None listed