A Study of ZN-c3 in Participants With Solid Tumors

K-Group Beta

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor

Treatments: Drug: ZN-c3

Study type: Interventional

Funder types: Industry

Identifiers

NCT04158336

ZN-c3-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 146 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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146 participants in 3 patient groups

Single Agent Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: ZN-c3

Single Agent Food Effect Cohort

Experimental group

Description:

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.

Treatment:

Drug: ZN-c3

Single Agent Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: ZN-c3