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

NCT ID: NCT03821233

Last Updated: 2025-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-15

Study Completion Date

2024-10-08

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

HER2-expressing Cancers

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

ZW49

Group Type EXPERIMENTAL

ZW49

Intervention Type DRUG

* 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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 Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Zymeworks BC Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Joseph Woolery, PharmD, BCOP

Role: STUDY_DIRECTOR

Zymeworks BC Inc.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope

Duarte, California, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of Chicago Medicine

Chicago, Illinois, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

NEXT Oncology

San Antonio, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Flinders Medical Centre

Adelaide, , Australia

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Canada South Korea

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ZWI-ZW49-101

Identifier Type: -

Identifier Source: org_study_id