Clinical Trials /

A Study of ZN-c3 in Participants With Solid Tumors

NCT04158336

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.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ZN-c3 in Participants With Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ZN-c3-001
  • NCT ID: NCT04158336

Conditions

  • 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

Interventions

DrugSynonymsArms
ZN-c3Study DrugSingle Agent Dose Escalation
TalazoparibTalzennaCombination with Talazoparib Phase 2
PembrolizumabKeytrudaCombination with Pembrolizumab Phase 2

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Single Agent Dose EscalationExperimentalParticipants 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.
  • ZN-c3
Single Agent Phase 2ExperimentalParticipants with specific types of solid tumors.
  • ZN-c3
Combination with Talazoparib Phase 2ExperimentalParticipants with a specific type of locally advanced or metastatic breast cancer.
  • ZN-c3
  • Talazoparib
Combination with Pembrolizumab Phase 2ExperimentalParticipants with specific types of solid tumors.
  • ZN-c3
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Incidence and severity of adverse events (AEs); Incidence and severity of dose-limiting toxicities (DLTs) in DLT-evaluable participants during Cycle 1

Secondary Outcome Measures

Measure:Preliminary estimates of antitumor efficacy of single agent ZN-c3
Time Frame:Through Phase 1, an average of 1 year
Safety Issue:
Description:Efficacy as defined by RECIST version 1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:K-Group Beta

Trial Keywords

  • Solid tumor

Last Updated

November 21, 2019