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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03821233




Registration number
NCT03821233
Ethics application status
Date submitted
28/01/2019
Date registered
29/01/2019
Date last updated
11/12/2023

Titles & IDs
Public title
A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers
Scientific title
A Phase 1 Study of ZW49 in Patients With Locally Advanced (Unresectable) or Metastatic HER2-Expressing Cancers
Secondary ID [1] 0 0
ZWI-ZW49-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2-expressing Cancers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZW49

Experimental: ZW49 -


Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to 4 weeks
Primary outcome [2] 0 0
Incidence of adverse events
Timepoint [2] 0 0
Up to 7 months
Primary outcome [3] 0 0
Incidence of lab abnormalities
Timepoint [3] 0 0
Up to 7 months
Primary outcome [4] 0 0
Incidence of electrocardiogram (ECG) and left ventricular ejection fraction (LVEF) abnormalities
Timepoint [4] 0 0
Up to 7 months
Primary outcome [5] 0 0
Incidence of dose reductions of ZW49
Timepoint [5] 0 0
Up to 7 months
Secondary outcome [1] 0 0
Serum concentrations of ZW49
Timepoint [1] 0 0
Up to 7 months
Secondary outcome [2] 0 0
Incidence of anti-drug antibodies (ADAs)
Timepoint [2] 0 0
Up to 7 months
Secondary outcome [3] 0 0
Objective response rate (ORR)
Timepoint [3] 0 0
Up to 6 months
Secondary outcome [4] 0 0
Disease control rate
Timepoint [4] 0 0
Up to 6 months
Secondary outcome [5] 0 0
Duration of response
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
Progression-free survival
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
Overall survival
Timepoint [7] 0 0
Up to 2 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/04/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2025
Actual
Sample size
Target
174
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Adelaide
Recruitment postcode(s) [1] 0 0
5042 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seongnam-si
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Zymeworks BC Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03821233
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joseph Woolery, PharmD, BCOP
Address 0 0
Zymeworks BC Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03821233