A Study of ZN-c3 in Participants With Solid Tumors

Sponsor

K-Group Beta (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04158336

Collaborator

(none)

110

Enrollment

Locations

Arm

Anticipated Duration (Months)

27.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1/2 open-label, multicenter study, evaluating the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics of ZN-c3 alone and in combination with other drugs.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Epithelial Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer Triple Negative Breast Cancer Small Cell Lung Cancer Metastatic Breast Cancer Malignant Melanoma Non Small Cell Lung Cancer Urothelial Carcinoma	Drug: ZN-c3	Phase 1

Detailed Description

This is a Phase 1/2 open-label, multicenter study, evaluating the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics of ZN-c3 alone and in combination with other drugs. This study consists of Phase 1 and Phase 2 components in participants with solid tumors.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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 :

Nov 1, 2019

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Agent Dose Escalation and Expansion Participants 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 Names: Study Drug

Arm

Intervention/Treatment

Experimental: Single Agent Dose Escalation and Expansion

Participants 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 Names:

Study Drug

Outcome Measures

Primary Outcome Measures

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). [Through completion, an average of 1 year]
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 dose-limiting toxicities (DLTs) in DLT-evaluable participants. [Through Cycle 1 (each cycle is 21 days), an average of 1 year]
Clinical activity of WEE1 inhibition by ZN-c3 at RP2D in subjects with uterine serous carcinoma. [Through completion, approximately 43 months]
Objective response rate (ORR) based on RECIST version 1.1

Secondary Outcome Measures

Preliminary estimates of antitumor efficacy of single agent ZN-c3 [Through completion, an average of 1 year]
Efficacy as defined by RECIST version 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

In order to be eligible to participate in any phase of this study, an individual must meet all of the following criteria:

Provision of written informed consent.
Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
Adequate hematologic and organ function as defined by the following criteria:
Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; excluding measurements obtained within 7 days after daily administration of filgrastim/sargramostim or within 3 weeks after administration of pegfilgrastim.
Platelet count ≥ 100 × 10^9/L; excluding measurements obtained within 3 days after transfusion of platelets.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastases, AST and ALT ≤ 5 x ULN.
Total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of Gilbert's disease.
Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min.
Female subjects of childbearing potential must have a negative serum beta human chorionic gonadotropin test.
Male subjects and female subjects of childbearing potential must agree to use an effective method of contraception per institutional standard prior to the first dose and for 90 days after the last dose of ZN-c3.

Individuals must meet the additional criteria in order to be eligible to participate in

Phase 1:

Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Measurable or evaluable disease per RECIST version 1.1.

Individuals must meet these additional criteria in order to be eligible to participate in

Phase 2 Single Agent part of the study:

ECOG performance status ≤ 1.
Measurable disease per RECIST version 1.1.

Individuals must meet these additional criteria in order to be eligible to participate in

Phase 2 combination with a PARP inhibitor:

ECOG performance status ≤ 1.
Measurable disease per RECIST version 1.1.

Individuals must meet these additional criteria in order to be eligible to participate in

Phase 2 combination with a PD-1 inhibitor:

ECOG performance status ≤ 1.
Measurable disease per RECIST version 1.1.

Key Exclusion Criteria:

Any of the following treatment interventions within the specified time frame prior to

Cycle 1 Day 1:

Major surgery within 28 days.
Radiation therapy within 21 days.
Any prior systemic therapy regardless of the stop date, but the subject must have recovered to eligibility levels from prior toxicity.
Autologous or allogeneic stem cell transplant within 3 months.
Current use of an investigational agent that is not expected to be cleared by the first dosing of study drug or that has demonstrated to have prolonged side effects. Subjects should have recovered from the side effects to a Grade 0 or 1 (except alopecia).
A serious illness or medical condition(s) including, but not limited to, the following:
Brain metastases that require immediate treatment or are clinically or radiologically unstable.
Leptomeningeal disease that requires or is anticipated to require immediate treatment.
Myocardial impairment of any cause resulting in heart failure by New York Heart Association Criteria Class III or IV.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the subject inappropriate for entry into this study.
Significant gastrointestinal abnormalities
Active or uncontrolled infection.
Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2 neuropathy, alopecia or skin pigmentation).
Prior therapy with ZN-c3 or known hypersensitivity to any drugs similar to ZN-c3 in class.
Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 0102	Tucson	Arizona	United States	85719
2	Site 0101	Detroit	Michigan	United States	48201
3	Site 0103	Houston	Texas	United States	77030
4	Site 0100	San Antonio	Texas	United States	78229