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
- Conditions
- Metastatic HER2-positive Breast Cancer
- Interventions
- Registration Number
- NCT06435429
- Lead Sponsor
- Jazz Pharmaceuticals
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 550
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trastuzumab plus physician's choice of chemotherapy Trastuzumab 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). Trastuzumab plus physician's choice of chemotherapy Eribulin 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). Zanidatamab plus physician's choice of chemotherapy Eribulin 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). Zanidatamab plus physician's choice of chemotherapy Capecitabine 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). Trastuzumab plus physician's choice of chemotherapy Vinorelbine 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). Trastuzumab plus physician's choice of chemotherapy Gemcitabine 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). Trastuzumab plus physician's choice of chemotherapy Capecitabine 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). Zanidatamab plus physician's choice of chemotherapy Zanidatamab 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). Zanidatamab plus physician's choice of chemotherapy Vinorelbine 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). Zanidatamab plus physician's choice of chemotherapy Gemcitabine 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).
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per RECIST Version 1.1 As Assessed by Blinded Independent Central Review (BICR) Until disease progression or death, up to approximately 44 months 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Until death, up to approximately 80 months OS is defined as the time in months from randomization to the date of death due to any cause.
Confirmed Objective Response Rate (ORR) Per RECIST Version 1.1, As Assessed by BICR Until disease progression or death, up to approximately 44 months 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.
Duration of Response (DOR) Per RECIST Version 1.1, As Assessed by BICR Until disease progression or death, up to approximately 44 months 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.
PFS Per RECIST Version 1.1, As Assessed By Investigator Until disease progression or death, up to approximately 44 months 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
Confirmed ORR Per RECIST Version 1.1, As Assessed By Investigator Until disease progression or death, up to approximately 44 months 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.
DOR Per RECIST Version 1.1, As Assessed By Investigator Until disease progression or death, up to approximately 44 months 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.
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events As Graded by NCI CTCAE Version 5.0 Up to approximately 44 months Number of Participants With Dose Reductions Up to approximately 44 months Number of Participants Discontinuing Study Treatment Due to TEAEs Up to approximately 44 months Serum Concentrations of Zanidatamab Up to approximately 44 months Number of Participants Positive for Anti-drug Antibodies to Zanidatamab 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 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) Up to approximately 44 months 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.
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) Up to approximately 44 months 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.
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Trial Locations
- Locations (159)
Mayo Clinic Scottsdale - PPDS
🇺🇸Phoenix, Arizona, United States
Arizona Oncology Tucson - Wilmot
🇺🇸Tucson, Arizona, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
The Oncology Institute Of Hope And Innovation
🇺🇸Cerritos, California, United States
Los Angeles Hematology Oncology Medical Group Glendale
🇺🇸Glendale, California, United States
USC-Norris Comprehensive Cancer Center - Investigational Drug Service IDS
🇺🇸Los Angeles, California, United States
UCSF at Mission Bay MB
🇺🇸San Francisco, California, United States
University of Colorado-Cancer Center-PPDS
🇺🇸Aurora, Colorado, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Medstar Georgetown University Hospital
🇺🇸Washington D.C., District of Columbia, United States
Scroll for more (149 remaining)Mayo Clinic Scottsdale - PPDS🇺🇸Phoenix, Arizona, United States