NCT06435429|RecruitingPhase 3DMCFDA Drug

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

A Phase 3, Randomized, Open-label, Multicenter, Controlled Study to Evaluate the Efficacy and Safety of Zanidatamab in Combination With Physician's Choice Chemotherapy Compared to Trastuzumab in Combination With Physician's Choice Chemotherapy for the Treatment of Participants With Metastatic HER2-positive Breast Cancer Who Have Progressed on, or Are Intolerant to, Previous Trastuzumab Deruxtecan Treatment

Jazz Pharmaceuticals ClinicalTrials.gov

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2 other identifiers

JZP598-3032023-508960-31-00

Study Type

interventional

Target

550

Locations

14 countries

Sites

160

Timeline

RegisteredMay 2024

StartedAug 2024

CompletionOct 2030

Brief Summary

The efficacy and safety of zanidatamab in combination with physician's choice of chemotherapy compared with trastuzumab in combination with physician's choice of chemotherapy will be evaluated for the treatment of participants with metastatic HER2-positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

550

participants targeted

Target at P75+ for phase_3

Timeline

54mo left

Started Aug 2024

Longer than P75 for phase_3

Geographic Reach

14 countries

160 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.2 years study duration

Study Progress28%

Aug 2024Oct 2030

First Submitted

Initial submission to the registry

May 24, 2024

Completed

6 days until next milestone

First Posted

Study publicly available on registry

May 30, 2024

Completed

3 months until next milestone

Study Start

First participant enrolled

August 13, 2024

Completed

3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 28, 2028

Expected

2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 18, 2030

Last Updated

February 10, 2026

Status Verified

February 1, 2026

Enrollment Period

3.7 years

First QC Date

May 24, 2024

Last Update Submit

February 6, 2026

Conditions

Metastatic HER2-positive Breast Cancer

Keywords

ZanidatamabTrastuzumabMetastatic HER2-positive breast cancer

Outcome Measures

Primary Outcomes (1)

Progression-free Survival (PFS) Per RECIST Version 1.1 As Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time in months from randomization to the date of first documented disease progression (as assessed by BICR according to RECIST v1.1) or death from any cause, whichever occurs first.
Until disease progression or death, up to approximately 44 months

Secondary Outcomes (14)

Overall Survival (OS)
Until death, up to approximately 80 months
Confirmed Objective Response Rate (ORR) Per RECIST Version 1.1, As Assessed by BICR
Until disease progression or death, up to approximately 44 months
Duration of Response (DOR) Per RECIST Version 1.1, As Assessed by BICR
Until disease progression or death, up to approximately 44 months
PFS Per RECIST Version 1.1, As Assessed By Investigator
Until disease progression or death, up to approximately 44 months
Confirmed ORR Per RECIST Version 1.1, As Assessed By Investigator
Until disease progression or death, up to approximately 44 months
+9 more secondary outcomes

Study Arms (2)

Zanidatamab plus physician's choice of chemotherapy

EXPERIMENTAL

Participants with HER2-positive metastatic breast cancer (mBC) who have progressed on, or are intolerant to, previous T-DXd treatment will be randomized to receive intravenous infusion of zanidatamab plus physician's choice of chemotherapy (eribulin, or vinorelbine, or gemcitabine, or capecitabine).

Drug: ZanidatamabDrug: EribulinDrug: VinorelbineDrug: GemcitabineDrug: Capecitabine

Trastuzumab plus physician's choice of chemotherapy

ACTIVE COMPARATOR

Participants with HER2-positive metastatic breast cancer (mBC) who have progressed on, or are intolerant to, previous T-DXd treatment will be randomized to receive intravenous infusion of trastuzumab plus physician's choice of chemotherapy (eribulin, or gemcitabine, or vinorelbine, or capecitabine).

Drug: TrastuzumabDrug: EribulinDrug: VinorelbineDrug: GemcitabineDrug: Capecitabine

Interventions

ZanidatamabDRUG

Administered by intravenous infusion

Zanidatamab plus physician's choice of chemotherapy

TrastuzumabDRUG

Administered by intravenous infusion

Trastuzumab plus physician's choice of chemotherapy

VinorelbineDRUG

Administered by intravenous infusion

Trastuzumab plus physician's choice of chemotherapyZanidatamab plus physician's choice of chemotherapy

GemcitabineDRUG

Administered by intravenous infusion

Trastuzumab plus physician's choice of chemotherapyZanidatamab plus physician's choice of chemotherapy

CapecitabineDRUG

Given orally

Trastuzumab plus physician's choice of chemotherapyZanidatamab plus physician's choice of chemotherapy

EribulinDRUG

Administered by intravenous infusion

Trastuzumab plus physician's choice of chemotherapyZanidatamab plus physician's choice of chemotherapy

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

Participants are eligible to be included in the study only if all of the following criteria apply: 1. Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent. 2. Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidelines as evaluated by a sponsor-designated central laboratory 3. Participants with unresectable or metastatic HER2 positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment. 4. Must have received at least 2 lines of HER2-directed therapy for their metastatic disease. 1. Prior HER2-targeted neo-adjuvant or adjuvant therapy that resulted in relapse within 6 months of the completion of therapy will be considered a line of treatment for metastatic disease. 2. Based on the physician's choice, participants' eligibility, and institutional and local guidelines, participants may also have received post-T-DXd therapy, for example, a tucatinib-based regimen and/or T-DM1. 3. Participants must not have received more than 4 lines of HER2-directed therapy in the metastatic setting. 5. Has measurable disease per RECIST version 1.1. 6. Is eligible to receive one of the chemotherapy options listed in the physician's choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine). 7. Participants with history of treated or clinically inactive CNS metastases are eligible as specified in the protocol. 8. Has a life expectancy of at least 6 months, in the opinion of the investigator. 9. Has adequate hematologic parameters as defined in the protocol. 10. Has adequate hepatic function as specified in the protocol. 11. Has creatinine clearance ≥ 50 mL/minute as calculated per local institutional guidelines. 12. Has LVEF ≥ 50% as determined by either echocardiogram or MUGA obtained within 4 weeks before the first dose of study intervention. 13. Has ECOG performance status of 0 or 1. 14. Participant agrees to the following based on sex assigned at birth. 1. Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 7 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance/standard practice: * Refrain from donating fresh unwashed semen. * Use contraception as follows as specified in the protocol 2. Female participants: * A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: * Is a women of nonchildbearing potential OR * Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of \< 1% per year), with low user dependency during the study intervention period and for at least 7 months after the last dose of study intervention. * A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 3 days before the first dose of study intervention. * Additional requirements for pregnancy testing during and after study intervention are provided in the protocol. * The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 15. Is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the protocol. Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Has clinically confirmed leptomeningeal disease, in the opinion of the investigator. 2. Has uncontrolled or significant cardiovascular disease. 3. Has toxicity related to prior cancer therapy that has not resolved to ≤ Grade 1, with exceptions as stated in the protocol. 4. Has uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. 5. Has an infection with HIV-1 or HIV-2, with the exception of participants with well-controlled HIV. 6. Has active hepatitis B or C infection. 7. Has an active SARS-CoV-2 infection. Participants with prior infection that has resolved per local institutions' requirements and screening guidance are eligible. 8. Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab. 9. Is unable to receive trastuzumab treatment due to medical contraindications. 10. Has any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site. 11. Has any condition that would prevent treatment with the physician's choice of chemotherapy. 12. Has any issue or condition that in the opinion of the investigator would contraindicate the participant's participation in the study or confound the results of the study. Prior/Concomitant Therapy 13. Has a history of prior allogeneic bone marrow, stem cell, or solid organ transplantation. 14. The washout periods for prior anticancer therapies before randomization as specified in the protocol. 15. Has a history of trauma or major surgery within 4 weeks prior to randomization. Other Exclusions 16. Has a known hypersensitivity to any components of the study drugs, including chemotherapy. 17. Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Jazz Pharmaceuticalslead

Study Sites (166)

Mayo Clinic Scottsdale - PPDS

Phoenix, Arizona, 85054, United States

RECRUITING

Arizona Oncology Tucson - Wilmot

Tucson, Arizona, 85711, United States

WITHDRAWN

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

RECRUITING

The Oncology Institute Of Hope And Innovation

Cerritos, California, 90703, United States

RECRUITING

Los Angeles Hematology Oncology Medical Group Glendale

Glendale, California, 91204, United States

RECRUITING

USC-Norris Comprehensive Cancer Center - Investigational Drug Service IDS

Los Angeles, California, 90033, United States

RECRUITING

UCSF at Mission Bay MB

San Francisco, California, 94158, United States

RECRUITING

University of Colorado-Cancer Center-PPDS

Aurora, Colorado, 80045-2517, United States

RECRUITING

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

RECRUITING

Medstar Georgetown University Hospital

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

RECRUITING

Washington Cancer Center

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

RECRUITING

Florida Cancer Specialists Research South

Fort Myers, Florida, 33901, United States

RECRUITING

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224, United States

RECRUITING

Florida Cancer Specialists Research North

St. Petersburg, Florida, 33705, United States

RECRUITING

Florida Cancer Specialists Research East

West Palm Beach, Florida, 33401, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5418, United States

RECRUITING

Minnesota Oncology Hematology

Coon Rapids, Minnesota, 55433, United States

RECRUITING

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

RECRUITING

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

RECRUITING

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

RECRUITING

Memorial Sloan Kettering

Long Island City, New York, 11101, United States

RECRUITING

Perlmutter Cancer Center 160 E 34th St

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

RECRUITING

The Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

Columbia University Medical Center 161 Fort Washington

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

RECRUITING

Messino Cancer Center

Asheville, North Carolina, 28806, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27710-2000, United States

RECRUITING

UNC Central Investigational Drug Services

Morrisville, North Carolina, 27560, United States

RECRUITING

Oncology Hematology Care (OHC)

Cincinnati, Ohio, 45226, United States

RECRUITING

University Hospitals Cleveland Medical Center 11100 Euclid Ave

Cleveland, Ohio, 44106-1716, United States

WITHDRAWN

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology - Fort Worth

Fort Worth, Texas, 76104, United States

RECRUITING

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

Houston, Texas, 77030, United States

RECRUITING

Millennium Research and Clinical Development

Houston, Texas, 77090, United States

WITHDRAWN

Maryland Oncology Hematology Healing Way - USOR