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

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ClinicalTrials.gov Identifier: NCT03821233
Recruitment Status : Recruiting
First Posted : January 29, 2019
Last Update Posted : April 6, 2021
Sponsor:
Information provided by (Responsible Party):
Zymeworks Inc.

Tracking Information
First Submitted Date  ICMJE January 28, 2019
First Posted Date  ICMJE January 29, 2019
Last Update Posted Date April 6, 2021
Actual Study Start Date  ICMJE April 15, 2019
Estimated Primary Completion Date May 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
  • 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.
  • Incidence of adverse events [ Time Frame: Up to 7 months ]
    Number of participants who experienced an adverse event
  • 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.
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2019)
  • 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.
  • Incidence of adverse events [ Time Frame: Up to 7 months ]
    Number of participants who experienced an adverse event
  • 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.
  • Incidence of electrocardiogram (ECG) and left ventricular ejection fraction (LVEF) abnormalities [ Time Frame: Up to 7 months ]
    Number of participants who experienced an abnormal ECF or LVEF
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2019)
  • Serum concentrations of ZW49 [ Time Frame: Up to 7 months ]
    End of infusion concentration, maximum serum concentration, and trough concentration of ZW49
  • Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 7 months ]
    Number of participants who develop ADAs
  • 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
  • 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
  • Duration of response [ Time Frame: Up to 2 years ]
    Median duration of response (in months) and range (minimum, maximum)
  • Progression-free survival [ Time Frame: Up to 2 years ]
    Median progression-free survival (in months) and range (minimum, maximum)
  • Overall survival [ Time Frame: Up to 2 years ]
    Median overall survival (in months) and range (minimum, maximum)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers
Official Title  ICMJE A Phase 1 Study of ZW49 in Patients With Locally Advanced (Unresectable) or Metastatic HER2-Expressing Cancers
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-expressing Cancers
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: ZW49
Intervention: Drug: ZW49
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2020)
174
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2019)
69
Estimated Study Completion Date  ICMJE April 30, 2023
Estimated Primary Completion Date May 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zymeworks Clinical Trial Resource (206) 237-1030 medinfo@zymeworks.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03821233
Other Study ID Numbers  ICMJE ZWI-ZW49-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zymeworks Inc.
Study Sponsor  ICMJE Zymeworks Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Joseph Woolery, PharmD, BCOP Zymeworks Inc.
PRS Account Zymeworks Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP