Clinical Trials /

A Study of ZW25 With Palbociclib Plus Fulvestrant in Patients With HER2+/HR+ Advanced Breast Cancer

NCT04224272

Description:

This is a multicenter, Phase 2a, open-label, 2-part study to investigate the safety, tolerability, and anti-tumor activity of ZW25 in combination with palbociclib plus fulvestrant. Eligible patients include those with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor (HR)-positive breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ZW25 With Palbociclib Plus Fulvestrant in Patients With HER2+/HR+ Advanced Breast Cancer
  • Official Title: Phase 2a Study of ZW25 in Combination With Palbociclib Plus Fulvestrant

Clinical Trial IDs

  • ORG STUDY ID: ZWI-ZW25-202
  • SECONDARY ID: 2019-002956-18
  • NCT ID: NCT04224272

Conditions

  • HER2+/HR+ Breast Cancer

Interventions

DrugSynonymsArms
ZW25ZW25 + palbociclib + fulvestrant
PalbociclibZW25 + palbociclib + fulvestrant
FulvestrantZW25 + palbociclib + fulvestrant

Purpose

This is a multicenter, Phase 2a, open-label, 2-part study to investigate the safety, tolerability, and anti-tumor activity of ZW25 in combination with palbociclib plus fulvestrant. Eligible patients include those with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor (HR)-positive breast cancer.

Detailed Description

      Part 1 of the study will first evaluate the safety and tolerability of ZW25 in combination
      with palbociclib plus fulvestrant and will confirm the recommended doses (RDs) of ZW25 and
      palbociclib in this combination. Part 2 of the study will evaluate the anti-tumor activity of
      the RD level of the combination of ZW25 with palbociclib plus fulvestrant in patients with
      HER2-positive, HR-positive advanced breast cancer.
    

Trial Arms

NameTypeDescriptionInterventions
ZW25 + palbociclib + fulvestrantExperimentalZW25 plus pabociclib, fulvestrant
  • ZW25
  • Palbociclib
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically-confirmed diagnosis of breast cancer with evidence of locally advanced
             (unresectable) and/or metastatic disease. All patients in both Parts 1 and 2 must have
             HER2-positive and HR-positive disease.

          -  Disease that has progressed or been refractory to prior treatment with trastuzumab,
             pertuzumab, AND ado-trastuzumab emtansine (T-DM1). Patients in any part of the study
             who did not receive pertuzumab or T-DM1 because of lack of access (e.g., due to
             insurance coverage or because they were treated prior to regulatory agency approval of
             the agent in a relevant indication) or due to medical ineligibility for treatment with
             T-DM1 (e.g., history of severe infusion reactions to trastuzumab, >/= Grade 2
             peripheral neuropathy, or platelet count < 100 x 10^9/L) may be eligible for the
             study. Prior treatment with endocrine therapy in the neoadjuvant, adjuvant, and/or
             metastatic setting is permitted.

          -  Sites of disease assessible per RECIST version 1.1 (both measurable and non-measurable
             disease allowed)

          -  An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

          -  Adequate organ function

          -  Adequate cardiac left ventricular function, as defined by a left ventricular ejection
             fraction (LVEF) >/= institutional standard of normal

        Exclusion Criteria:

          -  Prior treatment with trastuzumab, pertuzumab, lapatinib, T-DM1, or other
             anti-HER2-targeted therapy </= 3 weeks before the first dose of ZW25

          -  Prior treatment with chemotherapy, other anti-cancer therapy not otherwise specified,
             or hormonal cancer therapy </= 3 weeks before the first dose of ZW25

          -  Prior treatment with palbociclib or any other CDK4/6 inhibitor, including experimental
             agents

          -  History of myocardial infarction or unstable angina within 6 months prior to
             enrollment, troponin levels consistent with myocardial infarction, or clinically
             significant cardiac disease, such as ventricular arrhythmia requiring therapy,
             uncontrolled hypertension, or any history of symptomatic congestive heart failure
             (CHF)

          -  QTc Fridericia (QTcF) > 450 ms

          -  Grade 2 or greater pneumonitis and/or interstitial lung disease, including pulmonary
             fibrosis, or other clinically significant infiltrative pulmonary disease not related
             to lung metastases

          -  Active hepatitis B or hepatitis C infection

          -  Acute or chronic uncontrolled renal disease, pancreatitis, or severe liver disease
             (Child-Pugh Class C)

          -  Known infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception:
             patients with well controlled-HIV [e.g., cluster of differentiation 4 (CD4)-positive
             T-cell count > 350 mm3 and undetectable viral load] are eligible.)

          -  Prior or concurrent malignancy whose natural history or treatment has the potential to
             interfere with the safety or efficacy assessment of the investigational regimen

          -  Brain metastases: Untreated central nervous system (CNS) metastases, symptomatic CNS
             metastases, or radiation treatment for CNS metastases within 4 weeks of start of study
             treatment. Stable, treated brain metastases are allowed (defined as patients who are
             off steroids and anticonvulsants and are neurologically stable for at least 1 month at
             the time of screening).

          -  Known leptomeningeal disease (LMD)

          -  Grade 3 or greater peripheral neuropathy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities (DLTs; Part 1)
Time Frame:Up to 4 weeks
Safety Issue:
Description:Number of participants who experienced a DLT. DLTs include adverse events (AEs) considered to be related to ZW25, including combination of ZW25 with palbociclib and/or fulvestrant

Secondary Outcome Measures

Measure:Maximum serum concentration of ZW25 (Parts 1 and 2)
Time Frame:Up to 9 months
Safety Issue:
Description:
Measure:Trough concentration of ZW25 (Parts 1 and 2)
Time Frame:Up to 9 months
Safety Issue:
Description:Minimum observed serum concentration (trough)
Measure:Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2)
Time Frame:Up to 10 months
Safety Issue:
Description:Number of participants who develop ADAs
Measure:Objective response rate (Part 2)
Time Frame:Up to 3.5 years
Safety Issue:
Description:Number of participants who achieved a best response of either complete or partial response during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and as assessed by the investigator
Measure:Duration of response (Part 2)
Time Frame:Up to 3.5 years
Safety Issue:
Description:Median duration of response
Measure:Disease control rate (Part 2)
Time Frame:Up to 3.5 years
Safety Issue:
Description:Number of participants who achieved a best response of complete response, partial response, or stable disease during treatment according to the RECIST version 1.1 and as assessed by the investigator
Measure:Progression-free survival (PFS; Part 2)
Time Frame:Up to 3.5 years
Safety Issue:
Description:Median PFS
Measure:Incidence of AEs (Part 2)
Time Frame:Up to 3.5 years
Safety Issue:
Description:Number of participants who experienced AEs, SAEs, or AESIs
Measure:Incidence of lab abnormalities (Part 2)
Time Frame:Up to 3.5 years
Safety Issue:
Description:Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline lab abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's CTCAE, version 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Zymeworks Inc.

Trial Keywords

  • HER2
  • HR
  • Bispecific antibody
  • Biparatopic antibody
  • Immunotherapy
  • Breast cancer
  • Chemotherapy
  • Palbociclib
  • Fulvestrant

Last Updated

January 8, 2020