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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06435429




Registration number
NCT06435429
Ethics application status
Date submitted
24/05/2024
Date registered
30/05/2024
Date last updated
18/06/2025

Titles & IDs
Public 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
Scientific title
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
Secondary ID [1] 0 0
2023-508960-31-00
Secondary ID [2] 0 0
JZP598-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic HER2-positive Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zanidatamab
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Eribulin
Treatment: Drugs - Vinorelbine
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Capecitabine

Experimental: Zanidatamab plus physician's choice of chemotherapy - 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).

Active comparator: Trastuzumab plus physician's choice of chemotherapy - 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).


Treatment: Drugs: Zanidatamab
Administered by intravenous infusion

Treatment: Drugs: Trastuzumab
Administered by intravenous infusion

Treatment: Drugs: Eribulin
Administered by intravenous infusion

Treatment: Drugs: Vinorelbine
Administered by intravenous infusion

Treatment: Drugs: Gemcitabine
Administered by intravenous infusion

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per RECIST Version 1.1 As Assessed by Blinded Independent Central Review (BICR)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Until disease progression or death, up to approximately 44 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Assessment method [1] 0 0
OS is defined as the time in months from randomization to the date of death due to any cause.
Timepoint [1] 0 0
Until death, up to approximately 80 months
Secondary outcome [2] 0 0
Confirmed Objective Response Rate (ORR) Per RECIST Version 1.1, As Assessed by BICR
Assessment method [2] 0 0
The BICR-assessed confirmed ORR is defined as the proportion of participants who had a best overall response of BICR-assessed Complete Response (CR) or Partial Response (PR) after randomization.
Timepoint [2] 0 0
Until disease progression or death, up to approximately 44 months
Secondary outcome [3] 0 0
Duration of Response (DOR) Per RECIST Version 1.1, As Assessed by BICR
Assessment method [3] 0 0
BICR-assessed DOR is defined as the time in months from the first objective response (CR or PR) that is subsequently confirmed to documented progressive disease (PD) as assessed by BICR per RECIST v1.1 or death from any cause.
Timepoint [3] 0 0
Until disease progression or death, up to approximately 44 months
Secondary outcome [4] 0 0
PFS Per RECIST Version 1.1, As Assessed By Investigator
Assessment method [4] 0 0
Investigator-assessed PFS is defined as the time in months from randomization to the date of first documented disease progression (as assessed by investigator according to RECIST v1.1) or death from any cause, whichever occurs first
Timepoint [4] 0 0
Until disease progression or death, up to approximately 44 months
Secondary outcome [5] 0 0
Confirmed ORR Per RECIST Version 1.1, As Assessed By Investigator
Assessment method [5] 0 0
The investigator-assessed confirmed ORR is defined as the proportion of participants who had a best overall response of investigator-assessed confirmed CR or PR after randomization.
Timepoint [5] 0 0
Until disease progression or death, up to approximately 44 months
Secondary outcome [6] 0 0
DOR Per RECIST Version 1.1, As Assessed By Investigator
Assessment method [6] 0 0
Investigator-assessed DOR is defined as the time in months from the first objective response (CR or PR) that is subsequently confirmed to documented PD as assessed by the investigator per RECIST v1.1 or death from any cause.
Timepoint [6] 0 0
Until disease progression or death, up to approximately 44 months
Secondary outcome [7] 0 0
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events As Graded by NCI CTCAE Version 5.0
Assessment method [7] 0 0
Timepoint [7] 0 0
Up to approximately 44 months
Secondary outcome [8] 0 0
Number of Participants With Dose Reductions
Assessment method [8] 0 0
Timepoint [8] 0 0
Up to approximately 44 months
Secondary outcome [9] 0 0
Number of Participants Discontinuing Study Treatment Due to TEAEs
Assessment method [9] 0 0
Timepoint [9] 0 0
Up to approximately 44 months
Secondary outcome [10] 0 0
Serum Concentrations of Zanidatamab
Assessment method [10] 0 0
Timepoint [10] 0 0
Up to approximately 44 months
Secondary outcome [11] 0 0
Number of Participants Positive for Anti-drug Antibodies to Zanidatamab
Assessment method [11] 0 0
Timepoint [11] 0 0
Up to approximately 44 months
Secondary outcome [12] 0 0
Proportion of All Treated Participants, As Treated, Reporting Symptomatic Adverse Events While On Treatment Based on Patient-reported Outcome-Common Terminology Criteria for AEs and European Organisation for Research and Treatment of Cancer Item Library
Assessment method [12] 0 0
Timepoint [12] 0 0
Up to approximately 44 months
Secondary outcome [13] 0 0
Proportion of All Treated Participants, As Treated, Reporting Overall Side-effect Bother on the Functional Assessment of Chronic Illness Therapy General Physical Item 5 (FACIT-GP5)
Assessment method [13] 0 0
The Functional Assessment of Chronic Illness Therapy (FACIT) GP5 Item score ranges from 0 (Not at all) to 4 (Very Much), where higher scores reflect greater bother from treatment side effects.
Timepoint [13] 0 0
Up to approximately 44 months
Secondary outcome [14] 0 0
Proportion of Treated Participants, As Treated, With Maintained or Improved Physical Function While On Treatment Based On The Physical Functioning Subscale of the EORTC Quality of Life Questionnaire Core Module (EORTC QLQ-C30)
Assessment method [14] 0 0
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core Module Physical Functioning score ranges from 0 to 100, where higher scores reflect better functioning.
Timepoint [14] 0 0
Up to approximately 44 months

Eligibility
Key inclusion criteria
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 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. Has measurable disease per RECIST version 1.1.
5. Is eligible to receive one of the chemotherapy options listed in the physician's choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine).
6. Participants with history of treated or clinically inactive CNS metastases are eligible as specified in the protocol.
7. Has a life expectancy of at least 6 months, in the opinion of the investigator.
8. Has adequate hematologic parameters as defined in the protocol.
9. Has adequate hepatic function as specified in the protocol.
10. Has creatinine clearance = 30 mL/minute as calculated per local institutional guidelines.
11. Has LVEF = 50% as determined by either echocardiogram or MUGA obtained within 4 weeks before the first dose of study intervention.
12. Has ECOG performance status of 0 or 1.
13. 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 5 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance/standard practice, whichever is longer:
* 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 5 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance/standard practice, whichever is longer.
* 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.
14. 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 known or suspected leptomeningeal disease.
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 known HIV infection.
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. Was treated with any local or systemic antineoplastic therapy (including hormonal therapies for breast cancer) or any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to randomization.
15. Has a history of trauma or major surgery within 4 weeks prior to randomization.

Other
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/11/2031
Actual
Sample size
Target
550
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Sunshine Coast University Private Hospital - Birtinya
Recruitment hospital [2] 0 0
Box Hill Hospital - Melbourne
Recruitment hospital [3] 0 0
Peninsula and South Eastern Haematology and Oncology Group - Mount Waverly
Recruitment hospital [4] 0 0
HPS Pharmacies - Adelaide - Adelaide
Recruitment hospital [5] 0 0
The Kinghorn Cancer Centre - Mt Kuring-gai
Recruitment hospital [6] 0 0
St John of God Hospital Subiaco - Subiaco
Recruitment postcode(s) [1] 0 0
4575 - Birtinya
Recruitment postcode(s) [2] 0 0
3128 - Melbourne
Recruitment postcode(s) [3] 0 0
3149 - Mount Waverly
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
2080 - Mt Kuring-gai
Recruitment postcode(s) [6] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
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Missouri
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United States of America
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New Jersey
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United States of America
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New York
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North Carolina
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Ohio
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Pennsylvania
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Tennessee
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United States of America
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Texas
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United States of America
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Virginia
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United States of America
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Washington
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Austria
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Linz
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Austria
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Wels
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Austria
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Wien
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Belgium
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Anderlecht
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Belgium
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Edegem
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Belgium
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Gilly
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Belgium
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Namur
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Belgium
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Roeselare
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Brazil
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Brasilia
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Brazil
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Ceara
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Brazil
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Porto Alegre
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Brazil
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Recife
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Brazil
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Salvador
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Brazil
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São Caetano do Sul
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Canada
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Montreal
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Canada
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Ottawa
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Canada
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Quebec
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Canada
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Toronto
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Canada
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Vancouver
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France
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Bordeaux Cedex
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France
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Caen
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Dijon
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Le Mans
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Toulouse
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France
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Villejuif
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Germany
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Berlin
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Germany
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Dortmund
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Greece
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Athens
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Greece
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Patra
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Greece
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Thessaloniki
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Italy
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Aviano
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Italy
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Bergamo
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Italy
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Bologna
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Italy
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Milano
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Italy
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Monza
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Italy
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Padova
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Italy
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Pavia
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Chiba-shi
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Chuo-ku
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Chuo-Ku
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Fukuoka-shi
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Fukushima
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Hidaka-shi
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Isesaki-shi
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Kagoshima-Shi
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Kyoto
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Nagoya-shi
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Okayama
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Osaka-Shi
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Sapporo-shi
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Tokyo
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Japan
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Yokohama-shi
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Korea, Republic of
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Cheonan-si
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Korea, Republic of
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Namdong-gu
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Poland
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Biala Podlaska
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Poland
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Bialystok
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Poland
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Kraków
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Poland
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Poznan
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Poland
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Warszawa
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Spain
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A Coruña
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Spain
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Badajoz
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Spain
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Barcelona
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Spain
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Elche
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Spain
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Granada
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Spain
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Madrid
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Spain
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San Cristóbal de La Laguna
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Spain
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Sevilla
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Spain
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Valencia
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Spain
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Vigo
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United Kingdom
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Bath
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United Kingdom
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Glasgow
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Oxford
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United Kingdom
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Jazz Pharmaceuticals
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trial Disclosure & Transparency
Address 0 0
Country 0 0
Phone 0 0
215-832-3750
Email 0 0
ClinicalTrialDisclosure@JazzPharma.com
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06435429