HER2-expressing CancersPhase 1NCT03821233
A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers
A Phase 1 study testing ZW49 in people with HER2-expressing Cancers, run by Zymeworks BC Inc. at 16 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-expressing Cancers
- What is being tested?
- ZW49
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 16 sitesin 4 countries
- Study dates
- 15 Apr 2019to 8 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
United States8 sites
University of Chicago Medicine
Chicago, Illinois, 60637
City of Hope
Duarte, California, 91010
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
NEXT Oncology
San Antonio, Texas, 78229
Moffitt Cancer Center
Tampa, Florida, 33612
South Korea5 sites
Seoul National University Bundang Hospital
Seongnam-si, 13620
Korea University Anam Hospital
Seoul, 02841
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Canada2 sites
Jewish General Hospital
Montreal, Quebec, H3T1E2
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 1 Study of ZW49 in Patients With Locally Advanced (Unresectable) or Metastatic HER2-Expressing Cancers
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.
Read the 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.
- Conditions
- HER2-expressing Cancers
- Being tested
- ZW49
- 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
- Medical subject headings
- Stomach Neoplasms, Esophageal Neoplasms, Neoplasms, Breast Neoplasms, Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZW49Drug
- 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 group | Role | What they receive |
|---|---|---|
| ZW49 | Experimental | Not described Receives: Drug: ZW49 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
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.
Measured: Up to 4 weeks
Incidence of adverse events
Number of participants who experienced an adverse event
Measured: Up to 7 months
Incidence of lab abnormalities
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.
Measured: Up to 7 months
Incidence of electrocardiogram (ECG) and left ventricular ejection fraction (LVEF) abnormalities
Number of participants who experienced an abnormal ECG or LVEF
Measured: Up to 7 months
Incidence of dose reductions of ZW49
Number of doses reduced and number of participants who require a dose reduction
Measured: Up to 7 months
Secondary outcomes (6)
Serum concentrations of ZW49
End of infusion concentration, maximum serum concentration, and trough concentration of ZW49
Measured: Up to 7 months
Incidence of anti-drug antibodies (ADAs)
Number of participants who develop ADAs
Measured: Up to 7 months
Objective response rate (ORR)
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
Measured: Up to 6 months
Disease control rate
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
Measured: Up to 6 months
Duration of response
Median duration of response (in months) and range (minimum, maximum)
Measured: Up to 2 years
Progression-free survival
Median progression-free survival (in months) and range (minimum, maximum)
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2019
- Study start15 Apr 2019
- Primary completion27 Sep 2024
- Study completion8 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-expressing CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zymeworks BC Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joseph Woolery, PharmD, BCOP, Study director, Zymeworks BC Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03821233
- Sponsor's protocol ID
- ZWI-ZW49-101
- Status last verified
- Jan 2025
- First submitted
- 28 Jan 2019
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of ZW49 in Patients With Locally Advanced (Unresectable) or Metastatic HER2-Expressing Cancers
- ClinicalTrials.gov ID
- NCT03821233
- Acronym / sponsor ID
- ZWI-ZW49-101
- Conditions
- HER2-expressing Cancers
- Keywords
- HER2, Bispecific antibody, Biparatopic antibody, Immunotherapy, Gastric cancers, Esophageal cancers, Gastroesophageal junction (GEJ) cancers, Breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Zymeworks BC Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 27 Sep 2024 (actual)
- Study completion
- 8 Oct 2024 (actual)
- First posted
- 29 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ZW49 | Experimental | Drug: ZW49 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Pathologically-confirmed diagnosis of breast cancer, gastroesophageal adenocarcinoma (GEA), or other HER2-expressing cancer with evidence of locally advanced (unresectable) and/or metastatic disease.
- 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
- Sites of disease assessible per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- ECOG performance status score of 0 or 1
- Adequate organ function
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | ZW49 |
Primary outcome
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
6 secondary outcomes
Serum concentrations of ZW49
Time frame: Up to 7 months
Incidence of anti-drug antibodies (ADAs)
Time frame: Up to 7 months
Objective response rate (ORR)
Time frame: Up to 6 months
Disease control rate
Time frame: Up to 6 months
Duration of response
Time frame: Up to 2 years
Progression-free survival
Time frame: Up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Individual participant dataSharing planned: No
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Disitamab Vedotin Plus Intravesical Mitomycin C in HER2-Expressing Intermediate- to High-Risk Non-Muscle-Invasive Bladder Cancer
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RecruitingPhase 3
Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Woolery, PharmD, BCOP study director
Zymeworks BC Inc.
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZW49 in people with HER2-expressing Cancers, run by Zymeworks BC Inc. at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, South Korea, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) (time frame: Up to 4 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.