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: November 25, 2019
• Sponsor: K-Group Beta
• Collaborator: IQVIA Biotech
• Information provided by (Responsible Party): K-Group Beta

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; Drug: Talazoparib; Drug: Pembrolizumab	Phase 1; Phase 2

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 (Clinical Trial)
• Estimated Enrollment: 360 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of ZN-c3 as a Single Agent and in Combination With Talazoparib or Pembrolizumab in Patients With Solid Tumors
• Estimated Study Start Date: November 2019
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: August 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single Agent Dose Escalation; 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 Name: Study Drug
Experimental: Single Agent Phase 2; Participants with specific types of solid tumors.	Drug: ZN-c3; ZN-c3 is a study drug; Other Name: Study Drug
Experimental: Combination with Talazoparib Phase 2; Participants with a specific type of locally advanced or metastatic breast cancer.	Drug: ZN-c3; ZN-c3 is a study drug; Other Name: Study Drug; Drug: Talazoparib; Talazoparib is an approved drug; Other Name: Talzenna
Experimental: Combination with Pembrolizumab Phase 2; Participants with specific types of solid tumors.	Drug: ZN-c3; ZN-c3 is a study drug; Other Name: Study Drug; Drug: Pembrolizumab; Pembrolizumab is an approved drug; Other Name: Keytruda

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of single agent ZN c3, including identification of the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) [ Time Frame: AEs through Phase 1 completion, an average of 1 year and DLTs through Cycle 1 (each cycle is 21 days) In Phase 1, an average of 1 year ]
   Incidence and severity of adverse events (AEs); Incidence and severity of dose-limiting toxicities (DLTs) in DLT-evaluable participants during Cycle 1
2. Objective response rate (ORR) of ZN c3 as a single agent and in combination with a PARP inhibitor and with a PD-1 inhibitor, respectively [ Time Frame: Through Phase 2 completion, an average of 2 years ]
   ORR as defined by RECIST version 1.1
3. Safety of ZN-c3 in combination with a PARP inhibitor and with a PD-1 inhibitor, respectively, including the determination of a RP2D for the combinations [ Time Frame: Through Phase 2 completion, an average of 2 years ]
   Incidence and severity of DLTs; Incidence and severity of AEs

Secondary Outcome Measures :

1. Preliminary estimates of antitumor efficacy of single agent ZN-c3 [ Time Frame: Through Phase 1, an average of 1 year ]
   Efficacy as defined by 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

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:

1. Provision of written informed consent.
2. Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.

3. Adequate hematologic and organ function as defined by the following criteria:

   1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; excluding measurements obtained within 7 days after daily administration of filgrastim/sargramostim or within 3 weeks after administration of pegfilgrastim.
   2. Platelet count ≥ 100 × 109/L; excluding measurements obtained within 3 days after transfusion of platelets.
   3. 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.
   4. Total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of Gilbert's disease.
   5. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min.
4. Female subjects of childbearing potential must have a negative serum beta human chorionic gonadotropin test.
5. 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:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
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:

1. ECOG performance status ≤ 1.
2. 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:

1. ECOG performance status ≤ 1.
2. 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:

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

Key Exclusion Criteria:

1. Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1:

   1. Major surgery within 28 days.
   2. Radiation therapy within 21 days.
   3. Any prior systemic therapy regardless of the stop date, but the subject must have recovered to eligibility levels from prior toxicity.
   4. Autologous or allogeneic stem cell transplant within 3 months.
   5. 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).

2. A serious illness or medical condition(s) including, but not limited to, the following:

   1. Brain metastases that require immediate treatment or are clinically or radiologically unstable.
   2. Leptomeningeal disease that requires or is anticipated to require immediate treatment.
   3. Myocardial impairment of any cause resulting in heart failure by New York Heart Association Criteria Class III or IV.
   4. 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.
   5. Significant gastrointestinal abnormalities
   6. Active or uncontrolled infection.
3. Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2 neuropathy, alopecia or skin pigmentation).
4. Prior therapy with ZN-c3 or known hypersensitivity to any drugs similar to ZN-c3 in class.
5. Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.

Contacts and Locations

Contacts

Contact: Project Director; 8582634333; info@zenopharma.com

Locations

United States, Arizona

Site 0102; Not yet recruiting

Tucson, Arizona, United States, 85719

United States, Michigan

Site 0101; Not yet recruiting

Detroit, Michigan, United States, 48201

United States, Texas

Site 0103; Not yet recruiting

Houston, Texas, United States, 77030

Site 0100; Recruiting

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

K-Group Beta

IQVIA Biotech

Investigators

• Study Director: Mieke Ptaszynski, MD; K-Group Beta

More Information

• Responsible Party: K-Group Beta
• ClinicalTrials.gov Identifier: NCT04158336 History of Changes
• Other Study ID Numbers: ZN-c3-001
• First Posted: November 8, 2019
• Last Update Posted: November 25, 2019
• Last Verified: November 2019

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:

Solid tumor

Additional relevant MeSH terms:

Breast Neoplasms; Lung Neoplasms; Melanoma; Small Cell Lung Carcinoma; Fallopian Tube Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Ovarian Epithelial; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms