Clinical Trials /

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

NCT03821233

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers
  • Official Title: A Phase 1 Study of ZW49 in Patients With Locally Advanced (Unresectable) or Metastatic HER2-Expressing Cancers

Clinical Trial IDs

  • ORG STUDY ID: ZWI-ZW49-101
  • NCT ID: NCT03821233

Conditions

  • HER2-expressing Cancers

Interventions

DrugSynonymsArms
ZW49ZW49

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ZW49Experimental
  • ZW49

Eligibility 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:

          -  Prior treatment with ZW25, the investigational HER2-targeted monoclonal antibody

          -  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)
      
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)
Time Frame:Up to 4 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Serum concentrations of ZW49
Time Frame:Up to 7 months
Safety Issue:
Description:End of infusion concentration, maximum serum concentration, and trough concentration of ZW49
Measure:Incidence of anti-drug antibodies (ADAs)
Time Frame:Up to 7 months
Safety Issue:
Description:Number of participants who develop ADAs
Measure:Objective response rate (ORR)
Time Frame:Up to 6 months
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
Measure:Disease control rate
Time Frame:Up to 6 months
Safety Issue:
Description: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
Measure:Duration of response
Time Frame:Up to 2 years
Safety Issue:
Description:Median duration of response (in months) and range (minimum, maximum)
Measure:Progression-free survival
Time Frame:Up to 2 years
Safety Issue:
Description:Median progression-free survival (in months) and range (minimum, maximum)
Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:Median overall survival (in months) and range (minimum, maximum)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Zymeworks Inc.

Trial Keywords

  • 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

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