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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04224272
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Zymeworks Inc.

Brief Summary:
This is a multicenter, Phase 2a, open-label, 2-part study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) 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.

Condition or disease Intervention/treatment Phase
HER2+/HR+ Breast Cancer Drug: ZW25 (Zanidatamab) Drug: Palbociclib Drug: Fulvestrant Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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 combination of ZW25 with palbociclib plus fulvestrant at the RD level in patients with HER2-positive, HR-positive advanced breast cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2a Study of ZW25 in Combination With Palbociclib Plus Fulvestrant
Actual Study Start Date : June 10, 2020
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: ZW25 (zanidatamab) + palbociclib + fulvestrant
ZW25 (zanidatamab) plus palbociclib, fulvestrant
Drug: ZW25 (Zanidatamab)
Administered intravenously

Drug: Palbociclib
Administered orally

Drug: Fulvestrant
Administered as an intramuscular injection




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicities (DLTs; Part 1) [ Time Frame: Up to 4 weeks ]
    Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW25, including combination of ZW25 with palbociclib and/or fulvestrant

  2. Incidence of AEs (Part 1) [ Time Frame: Up to 3.5 years ]
    Number of participants who experienced AEs, serious adverse events (SAEs), or adverse events of special interest (AESIs)

  3. Incidence of lab abnormalities (Part 1) [ Time Frame: Up to 3.5 years ]
    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 Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

  4. Progression-free survival 6 (PFS6; Part 2) [ Time Frame: Up to 6 months ]
    Percent of modified intent to treat patients with PFS greater than or equal to 24 weeks


Secondary Outcome Measures :
  1. Maximum serum concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 9 months ]
  2. Trough concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 9 months ]
    Minimum observed serum concentration (trough)

  3. Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2) [ Time Frame: Up to 10 months ]
    Number of participants who develop ADAs

  4. Objective response rate (Part 2) [ Time Frame: Up to 3.5 years ]
    Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and as assessed by the investigator

  5. Duration of response (Part 2) [ Time Frame: Up to 3.5 years ]
    Time from the first objective response (CR or PR) to documented progressive disease per RECIST 1.1 or death within 30 days of last dose of study drug (ZW25, palbociclib, and/or fulvestrant) from any cause

  6. Disease control rate (Part 2) [ Time Frame: Up to 3.5 years ]
    Number of participants who achieved a best response of CR, PR, or stable disease during treatment according to the RECIST version 1.1 and as assessed by the investigator

  7. Progression-free survival (PFS; Part 2) [ Time Frame: Up to 3.5 years ]
    Time from the first dose of ZW25, palbociclib, and/or fulvestrant to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause

  8. Overall survival (Part 2) [ Time Frame: Up to 3.5 years ]
    Time from the first dose of ZW25, palbociclib, and/or fulvestrant until death from any cause

  9. Incidence of AEs (Part 2) [ Time Frame: Up to 3.5 years ]
    Number of participants who experienced AEs, SAEs, or AESIs

  10. Incidence of lab abnormalities (Part 2) [ Time Frame: Up to 3.5 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • Received prior treatment with trastuzumab, pertuzumab, AND ado-trastuzumab emtansine (T-DM1); disease progression during or after the most recent prior therapy. 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 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) > 470 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).
  • History of or ongoing leptomeningeal disease
  • Grade 3 or greater peripheral neuropathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04224272


Contacts
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Contact: Zymeworks Clinical Trial Resource (206) 237-1030 medinfo@zymeworks.com

Locations
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United States, California
UCLA Hematology/Oncology Parkside Recruiting
Santa Monica, California, United States, 90404
Principal Investigator: Sara Hurvitz, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Erika Hamilton, MD         
United States, Texas
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Muralidhar Beeram, MD         
Canada, Ontario
The Ottawa Hospital Cancer Centre Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Principal Investigator: Marie-France Savard, MD         
Spain
Hospital General Universitario de Elche Recruiting
Elche, Alicante, Spain, 03203
Principal Investigator: Álvaro Rodriguez-Lescure, MD, PhD         
IOB-Hospital Quironsalud Barcelona Recruiting
Barcelona, Spain, 08023
Principal Investigator: José Manuel Pérez García, MD, PhD         
Hospital Universitario Vall d'Hebrón Recruiting
Barcelona, Spain, 08035
Principal Investigator: Santiago Escrivá de Romaní Muñoz, MD         
Hospital Ruber Internacional Recruiting
Madrid, Spain, 28034
Principal Investigator: Javier Cortés Castan, MD         
Hospital Universitario Virgen de la Victoria Recruiting
Málaga, Spain, 29010
Principal Investigator: Emilio Alba Conejo, MD, PhD         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Principal Investigator: Manuel Ruiz-Borrego, MD         
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Principal Investigator: Juan Miguel Cejalvo Andújar, MD         
Sponsors and Collaborators
Zymeworks Inc.
Investigators
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Study Director: Elaina Gartner, MD Zymeworks Inc.
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Responsible Party: Zymeworks Inc.
ClinicalTrials.gov Identifier: NCT04224272    
Other Study ID Numbers: ZWI-ZW25-202
2019-002956-18 ( EudraCT Number )
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zymeworks Inc.:
HER2
HR
Bispecific antibody
Biparatopic antibody
Immunotherapy
Breast cancer
Chemotherapy
Palbociclib
Fulvestrant
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Palbociclib
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action