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Trial record 1 of 4 for:    zw25
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A Study of ZW25 With Palbociclib Plus Fulvestrant in Patients With HER2+/HR+ Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT04224272
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : March 31, 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 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 Drug: Palbociclib Drug: Fulvestrant Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 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
Estimated Study Start Date : April 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 + palbociclib + fulvestrant
ZW25 plus pabociclib, fulvestrant
Drug: ZW25
Administered intravenous(ly) every 2 weeks (Q2W)

Drug: Palbociclib
Administered orally once daily

Drug: Fulvestrant
Administered as an intramuscular injection Q2W followed by every 4 weeks (Q4W)




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 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 evaluable 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 or partial response 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 ]
    Median duration of response

  6. Disease control rate (Part 2) [ Time Frame: Up to 3.5 years ]
    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

  7. Progression-free survival (PFS; Part 2) [ Time Frame: Up to 3.5 years ]
    Median PFS

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

  9. 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.



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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.
  • 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

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, 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         
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: March 31, 2020
Last Verified: March 2020

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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