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
PHASE3RECRUITING
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.
Study details:
Zanidatamab, as a monotherapy or in combination with other antineoplastic agents, has shown clinically meaningful efficacy against multiple HER2-positive advanced/metastatic tumors, including in patients with metastatic breast cancer (mBC). Zanidatamab may offer a viable treatment option for patients with metastatic HER2-positive breast cancer. The primary objective of the study is to compare the efficacy of zanidatamab plus chemotherapy versus trastuzumab plus chemotherapy.
The secondary objectives of the study will include further comparing the efficacy, safety and tolerability, patient-reported tolerability, and patient-reported physical functioning of zanidatamab plus chemotherapy versus trastuzumab plus chemotherapy. The pharmacokinetics and immunogenicity of zanidatamab in combination with chemotherapy will also be evaluated.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent.
- Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidelines as evaluated by a central laboratory.
- Participants with unresectable or metastatic HER2 positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment.
- Has measurable disease per RECIST version 1.1.
- Is eligible to receive one of the chemotherapy options listed in the physician's choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine).
- Participants with history of treated or clinically inactive CNS metastases are eligible as specified in the protocol.
- Has a life expectancy of at least 6 months, in the opinion of the investigator.
- Has adequate hematologic parameters as defined in the protocol.
- Has adequate hepatic function as specified in the protocol.
- Has creatinine clearance ≥ 30 mL/minute as calculated per local institutional guidelines.
- Has LVEF ≥ 50% as determined by either echocardiogram or MUGA obtained within 4 weeks before the first dose of study intervention.
- Has ECOG performance status of 0 or 1.
- Participant agrees to the following based on sex assigned at birth.
Exclusion criteria
- Has known or suspected leptomeningeal disease.
- Has uncontrolled or significant cardiovascular disease.
- Has toxicity related to prior cancer therapy that has not resolved to ≤ Grade 1, with exceptions as stated in the protocol.
- Has uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- Has known HIV infection.
- Has active hepatitis B or C infection.
- Has an active SARS-CoV-2 infection. Participants with prior infection that has resolved per local institutions' requirements and screening guidance are eligible.
- Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab.
- Is unable to receive trastuzumab treatment due to medical contraindications.
- 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.
- Has any condition that would prevent treatment with the physician's choice of chemotherapy.
- 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.
- Has a history of prior allogeneic bone marrow, stem cell, or solid organ transplantation.
- 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.
- Has a history of trauma or major surgery within 4 weeks prior to randomization.
- Has a known hypersensitivity to any components of the study drugs, including chemotherapy.
- Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06435429
Intervention or treatment
DRUG: Zanidatamab
DRUG: Trastuzumab
DRUG: Eribulin
DRUG: Vinorelbine
DRUG: Gemcitabine
DRUG: Capecitabine
Conditions
- Metastatic HER2-positive Breast Cancer
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Sunshine Coast University Private Hospital
Select from list below to view details:
Sunshine Coast University Private Hospital
Birtinya, Queensland, Australia
Box Hill Hospital
Melbourne, Victoria, Australia
Peninsula and South Eastern Haematology and Oncology Group
Mount Waverly, Victoria, Australia
HPS Pharmacies - Adelaide
Adelaide, Australia
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Who is running the clinical trial?
JP
Jazz Pharmaceuticals
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Zanidatamab plus physician's choice of chemotherapy
| Drug: Zanidatamab, Drug: Eribulin, Drug: Vinorelbine, Drug: Gemcitabine, Drug: Capecitabine |
ACTIVE_COMPARATOR: Trastuzumab plus physician's choice of chemotherapy
| Drug: Trastuzumab, Drug: Eribulin, Drug: Vinorelbine, Drug: Gemcitabine, Drug: Capecitabine |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | OS is defined as the time in months from randomization to the date of death due to any cause. | Until death, up to approximately 80 months |
| Confirmed Objective Response Rate (ORR) Per RECIST Version 1.1, As Assessed by BICR | 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. | Until disease progression or death, up to approximately 44 months |
| Duration of Response (DOR) Per RECIST Version 1.1, As Assessed by BICR | 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. | Until disease progression or death, up to approximately 44 months |
| PFS Per RECIST Version 1.1, As Assessed By Investigator | 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 | Until disease progression or death, up to approximately 44 months |
| Confirmed ORR Per RECIST Version 1.1, As Assessed By Investigator | 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. | Until disease progression or death, up to approximately 44 months |
| DOR Per RECIST Version 1.1, As Assessed By Investigator | 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. | Until disease progression or death, up to approximately 44 months |
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events As Graded by NCI CTCAE Version 5.0 | Not Specified | Up to approximately 44 months |
| Number of Participants With Dose Reductions | Not Specified | Up to approximately 44 months |
| Number of Participants Discontinuing Study Treatment Due to TEAEs | Not Specified | Up to approximately 44 months |
| Serum Concentrations of Zanidatamab | Not Specified | Up to approximately 44 months |
| Number of Participants Positive for Anti-drug Antibodies to Zanidatamab | Not Specified | Up to approximately 44 months |
| 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 | Not Specified | Up to approximately 44 months |
| 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) | 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. | Up to approximately 44 months |
| 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) | 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. | Up to approximately 44 months |
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References
Clinical Trials Gov: 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 CancerOther trials to consider
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