What is zanidatamab studying for metastatic HER2-positive breast cancer?

Zanidatamab is being studied to compare its effectiveness and safety with trastuzumab when each is combined with chemotherapy for treating metastatic HER2-positive breast cancer in patients who have progressed on or cannot tolerate previous trastuzumab deruxtecan treatment. This study aims to understand how zanidatamab works in this setting and its impact on patient health. The research is sponsored by Jazz Pharmaceuticals.

Who may be eligible for this metastatic HER2-positive breast cancer clinical trial?

Adults aged 18 or older with HER2-positive metastatic breast cancer who have progressed on or are intolerant to trastuzumab deruxtecan treatment may be eligible. Participants must have received at least two prior HER2-directed therapies and have a good performance status. This trial is open to all genders. Please review eligibility criteria for more details.

Is there any cost to participate in this metastatic HER2-positive breast cancer clinical trial?

Study-related care, including the study drugs and all trial visits, is provided at no cost. However, personal expenses such as travel may vary and are not guaranteed to be covered. Participants should plan accordingly for any additional costs.

Actively Recruiting

Phase 3

Age: 18Years +

All Genders

ID06435429

A Phase 3, Randomized, Open-label Study Comparing Zanidatamab Plus Chemotherapy to Trastuzumab Plus Chemotherapy for Metastatic HER2-positive Breast Cancer After Prior Trastuzumab Deruxtecan

Led by Jazz Pharmaceuticals · Updated on 2026-02-10

550

Participants Needed

166

Research Sites

129 weeks

Total Duration

AI-Summary

What this Trial Is About

This research aims to evaluate the effectiveness and safety of zanidatamab combined with a physician's choice of chemotherapy compared to trastuzumab combined with chemotherapy in treating adults with metastatic HER2-positive breast cancer who have either progressed on or cannot tolerate previous trastuzumab deruxtecan (T-DXd) treatment. Zanidatamab has shown promising results against various HER2-positive advanced tumors, including metastatic breast cancer, and may serve as a potential treatment option for these patients. The study also investigates patient-reported tolerability and physical functioning, as well as the pharmacokinetics and immune response to zanidatamab with chemotherapy. Participants will be randomly assigned to receive either zanidatamab or trastuzumab, each given by intravenous infusion alongside one of several chemotherapy options chosen by the physician: eribulin, vinorelbine, gemcitabine, or capecitabine (the latter is taken orally). Treatment will be administered according to the assigned group, and the study is open-label and multicenter, designed to compare these two treatment combinations in this patient population. During the study, participants will undergo regular assessments to monitor disease progression using imaging criteria (RECIST version 1.1), evaluate survival, treatment response, and duration of response. Safety and side effects will be tracked through adverse event reporting and patient questionnaires on symptoms and physical function. Blood samples will be collected to study drug levels and immune reactions. Participants will be followed until disease progression, death, or for up to approximately 44 months for key outcomes, with overall survival monitored for up to about 80 months.

CONDITIONS

Brief Title

A Study Comparing the Efficacy and Safety of Zanidatamab to Trastuzumab, Each in Combination With Physician's Choice Chemotherapy, for the Treatment of Participants With Metastatic HER2-positive Breast Cancer

Who Can Participate

Age: 18Years +

All Genders

Eligibility Criteria

You may qualify if you...

Is 18 years of age or older at the time of signing informed consent
Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidelines
Has unresectable or metastatic HER2-positive breast cancer that progressed on, or is intolerant to, previous trastuzumab deruxtecan treatment
Has received at least 2 lines of HER2-directed therapy for metastatic disease
Has measurable disease per RECIST version 1.1
Is eligible to receive one of the chemotherapy options: eribulin, gemcitabine, vinorelbine, or capecitabine
Has a history of treated or clinically inactive CNS metastases as specified in the protocol
Has a life expectancy of at least 6 months as judged by the investigator
Has adequate hematologic parameters as defined in the protocol
Has adequate liver function as specified in the protocol
Has creatinine clearance of at least 50 mL/min as per local guidelines
Has left ventricular ejection fraction (LVEF) of at least 50% by echocardiogram or MUGA within 4 weeks before first dose
Has an ECOG performance status of 0 or 1
Male participants agree to use contraception and avoid donating fresh unwashed semen during and for 7 months after treatment
Female participants are not pregnant or breastfeeding and either are of nonchildbearing potential or use highly effective contraception during and for 7 months after treatment
Female participants of childbearing potential must have a negative pregnancy test within 3 days before first dose
Is capable of giving signed informed consent and complying with study requirements

You will not qualify if you...

Has clinically confirmed leptomeningeal disease
Has uncontrolled or significant cardiovascular disease
Has unresolved toxicity from prior cancer therapy above Grade 1 except as stated in the protocol
Has uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals
Has HIV infection not well controlled
Has active hepatitis B or C infection
Has active SARS-CoV-2 infection
Has history of life-threatening hypersensitivity to monoclonal antibodies or zanidatamab components
Unable to receive trastuzumab due to medical contraindications
Has any serious medical or psychiatric condition impairing treatment tolerance
Has conditions preventing chemotherapy treatment
Has any issue that may contraindicate participation or confound study results
History of allogeneic bone marrow, stem cell, or solid organ transplantation
Recent trauma or major surgery within 4 weeks prior to randomization
Known hypersensitivity to study drugs or chemotherapy components
Female participants who are pregnant or breastfeeding
Female and male participants planning pregnancy during the study period

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Until disease progression or death, up to approximately 44 months

Participants receive zanidatamab plus chemotherapy or trastuzumab plus chemotherapy to treat metastatic HER2-positive breast cancer. The chemotherapy options include eribulin, vinorelbine, gemcitabine, or capecitabine.

Repeated visits for intravenous infusions and oral medication as per treatment schedule

Follow-up

Duration - Up to approximately 80 months

Participants are monitored for overall survival and long-term safety after treatment ends.

Periodic visits for survival and safety assessments

Trial Site Locations

Total: 166 locations

Mayo Clinic Scottsdale - PPDS

Phoenix, Arizona, United States, 85054

Actively Recruiting

Arizona Oncology Tucson - Wilmot

Tucson, Arizona, United States, 85711

Withdrawn

University of Arizona Cancer Center

Tucson, Arizona, United States, 85719

Actively Recruiting

The Oncology Institute Of Hope And Innovation

Cerritos, California, United States, 90703

Actively Recruiting

Los Angeles Hematology Oncology Medical Group Glendale

Glendale, California, United States, 91204

Actively Recruiting

USC-Norris Comprehensive Cancer Center - Investigational Drug Service IDS

Los Angeles, California, United States, 90033

Actively Recruiting

UCSF at Mission Bay MB

San Francisco, California, United States, 94158

Actively Recruiting

University of Colorado-Cancer Center-PPDS

Aurora, Colorado, United States, 80045-2517

Actively Recruiting

Rocky Mountain Cancer Centers

Denver, Colorado, United States, 80218

Actively Recruiting

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, United States, 20007

Actively Recruiting

Washington Cancer Center

Washington D.C., District of Columbia, United States, 20010

Actively Recruiting

Florida Cancer Specialists Research South

Fort Myers, Florida, United States, 33901

Actively Recruiting

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, United States, 32224

Actively Recruiting

Florida Cancer Specialists Research North

St. Petersburg, Florida, United States, 33705

Actively Recruiting

Florida Cancer Specialists Research East

West Palm Beach, Florida, United States, 33401

Actively Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215-5418

Actively Recruiting

Minnesota Oncology Hematology

Coon Rapids, Minnesota, United States, 55433

Actively Recruiting

Mayo Clinic - PPDS

Rochester, Minnesota, United States, 55905

Actively Recruiting

Saint Luke's Cancer Institute

Kansas City, Missouri, United States, 64111

Actively Recruiting

Hackensack Meridian Health

Hackensack, New Jersey, United States, 07601

Actively Recruiting

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08901

Actively Recruiting

Memorial Sloan Kettering

Long Island City, New York, United States, 11101

Actively Recruiting

Perlmutter Cancer Center 160 E 34th St

New York, New York, United States, 10016-4744

Actively Recruiting

The Mount Sinai Hospital

New York, New York, United States, 10029

Actively Recruiting

Columbia University Medical Center 161 Fort Washington

New York, New York, United States, 10032-3729

Actively Recruiting

Messino Cancer Center

Asheville, North Carolina, United States, 28806

Actively Recruiting

Duke Cancer Institute

Durham, North Carolina, United States, 27710-2000

Actively Recruiting

UNC Central Investigational Drug Services

Morrisville, North Carolina, United States, 27560

Actively Recruiting

Oncology Hematology Care (OHC)

Cincinnati, Ohio, United States, 45226

Actively Recruiting

University Hospitals Cleveland Medical Center 11100 Euclid Ave

Cleveland, Ohio, United States, 44106-1716

Withdrawn

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Actively Recruiting

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

Actively Recruiting

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

Actively Recruiting

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Actively Recruiting

Texas Oncology - Fort Worth

Fort Worth, Texas, United States, 76104

Actively Recruiting

U.T. MD Anderson Cancer Center, Investigational Pharmacy Services

Houston, Texas, United States, 77030

Actively Recruiting

Millennium Research and Clinical Development

Houston, Texas, United States, 77090

Withdrawn

Maryland Oncology Hematology Healing Way - USOR