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A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03821233
Recruitment Status : Active, not recruiting
First Posted : January 29, 2019
Last Update Posted : May 11, 2023
Sponsor:
Information provided by (Responsible Party):
Zymeworks Inc.

Study Description
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Brief Summary:
This is a first-in-human, Phase 1, multicenter, open-label, dose-escalation study to establish the maximum-tolerated dose (MTD) or recommended dosage (RD) of ZW49, the investigational agent under study, and to assess the safety and tolerability of ZW49. Eligible patients include those with locally advanced (unresectable) or metastatic HER2-expressing cancers.

Condition or disease Intervention/treatment Phase
HER2-expressing Cancers Drug: ZW49 Phase 1

Detailed Description:
The study will use a 3+3 dose-escalation study design to evaluate the safety and tolerability of ZW49 and to determine the MTD or RD of ZW49 for further study. Selected expansion cohorts will be subsequently opened based upon Safety Monitoring Committee (SMC) recommendation and sponsor approval to further evaluate the safety and tolerability of ZW49 at the MTD or RD and to assess preliminary anti-tumor activity.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: N/A
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of ZW49 in Patients With Locally Advanced (Unresectable) or Metastatic HER2-Expressing Cancers
Actual Study Start Date : April 15, 2019
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: ZW49 Drug: ZW49
  • Dose Escalation: ZW49 administered intravenously at dose levels determined by the SMC
  • Expansion: MTD or RD identified in the dose-escalation part of the study


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to 4 weeks ]
    Number of participants who experienced a DLT. DLTs are events that occur following administration of any amount of ZW49 and are considered related to ZW49 per the investigator. DLTs will include only events considered related to ZW49.

  2. Incidence of adverse events [ Time Frame: Up to 7 months ]
    Number of participants who experienced an adverse event

  3. Incidence of lab abnormalities [ Time Frame: Up to 7 months ]
    Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

  4. Incidence of electrocardiogram (ECG) and left ventricular ejection fraction (LVEF) abnormalities [ Time Frame: Up to 7 months ]
    Number of participants who experienced an abnormal ECG or LVEF

  5. Incidence of dose reductions of ZW49 [ Time Frame: Up to 7 months ]
    Number of doses reduced and number of participants who require a dose reduction


Secondary Outcome Measures :
  1. Serum concentrations of ZW49 [ Time Frame: Up to 7 months ]
    End of infusion concentration, maximum serum concentration, and trough concentration of ZW49

  2. Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 7 months ]
    Number of participants who develop ADAs

  3. Objective response rate (ORR) [ Time Frame: Up to 6 months ]
    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

  4. Disease control rate [ Time Frame: Up to 6 months ]
    Number of participants who achieved a best response of complete response, partial response, or stable disease during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  5. Duration of response [ Time Frame: Up to 2 years ]
    Median duration of response (in months) and range (minimum, maximum)

  6. Progression-free survival [ Time Frame: Up to 2 years ]
    Median progression-free survival (in months) and range (minimum, maximum)

  7. Overall survival [ Time Frame: Up to 2 years ]
    Median overall survival (in months) and range (minimum, maximum)


Eligibility Criteria
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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, gastroesophageal adenocarcinoma (GEA), or other HER2-expressing cancer with evidence of locally advanced (unresectable) and/or metastatic disease.

    • Dose-escalation (Cohort 1): HER2-high advanced solid tumors
    • Expansion (Cohort 2): HER2-high breast cancer
    • Expansion (Cohort 3): HER2-high GEA
    • Expansion (Cohort 4): HER2-high other non-breast and non-GEA cancers

  • Progressive disease that has progressed on or been refractory to all standard of care. Patients who were intolerant to or ineligible for standard therapy may be eligible if the reasons are carefully documented and approval is provided by the sponsor medical monitor

    • Patients with HER2-high breast cancer must have received prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1)
    • Patients with HER2-high GEA must have received prior treatment with trastuzumab

  • Sites of disease assessible per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    • Dose-escalation: measurable or non-measurable disease
    • Expansion: measurable disease
  • ECOG performance status score of 0 or 1
  • Adequate organ function
  • Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal

Exclusion Criteria:

  • 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)
  • Clinically significant infiltrative pulmonary disease not related to lung metastases
  • Active hepatitis B or hepatitis C infection or other known chronic liver disease
  • Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)
  • Known history of human immunodeficiency virus (HIV) infection
  • Brain metastases: Untreated 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 stable for at least 1 month at the time of screening).
  • Known leptomeningeal disease (LMD)
Contacts and Locations
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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): NCT03821233


Locations
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United States, California
City of Hope
Duarte, California, United States, 91010
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago Medicine
Chicago, Illinois, United States, 60637
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
NEXT Oncology
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Cancer Specialists, PC
Fairfax, Virginia, United States, 22031
Australia
Flinders Medical Centre
Adelaide, Australia, 5042
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T1E2
Korea, Republic of
Seoul National University Bundang Hospital
Seongnam-si, Korea, Republic of, 13620
Korea University Anam Hospital
Seoul, Korea, Republic of, 02841
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of, 03722
Asan Medical Center
Seoul, Korea, Republic of, 05505
Sponsors and Collaborators
Zymeworks Inc.
Investigators
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Study Director: Joseph Woolery, PharmD, BCOP Zymeworks Inc.
More Information
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Responsible Party: Zymeworks Inc.
ClinicalTrials.gov Identifier: NCT03821233    
Other Study ID Numbers: ZWI-ZW49-101
First Posted: January 29, 2019    Key Record Dates
Last Update Posted: May 11, 2023
Last Verified: May 2023
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
Bispecific antibody
Biparatopic antibody
Immunotherapy
Gastric cancers
Esophageal cancers
 Gastroesophageal junction (GEJ) cancers
Breast cancer
Ovarian cancer
Non-small cell lung cancer
Colorectal cancer
Cholangiocarcinoma