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.
Related Research Topics
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Trial Locations
- Locations (117)
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Canada
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
USC-Norris Comprehensive Cancer Center - Investigational Drug Service IDS
🇺🇸Los Angeles, 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, District of Columbia, United States
Washington Cancer Center
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists Research South
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists Research North
🇺🇸Saint Petersburg, Florida, United States
Florida Cancer Specialists Research East
🇺🇸West Palm Beach, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Minnesota Oncology Hematology
🇺🇸Coon Rapids, Minnesota, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Hackensack Meridian Health
🇺🇸Hackensack, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Perlmutter Cancer Center 160 E 34th St
🇺🇸New York, New York, United States
Columbia University Medical Center 161 Fort Washington
🇺🇸New York, New York, United States
Messino Cancer Center
🇺🇸Asheville, North Carolina, United States
Oncology Hematology Care (OHC)
🇺🇸Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center 11100 Euclid Ave
🇺🇸Cleveland, Ohio, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Texas Oncology - Fort Worth
🇺🇸Fort Worth, Texas, United States
Millennium Research and Clinical Development
🇺🇸Houston, Texas, United States
Maryland Oncology Hematology Healing Way - USOR
🇺🇸Irving, Texas, United States
Medical Oncology Hematology Consultants
🇺🇸Irving, Texas, United States
Nexus Health
🇺🇸Irving, Texas, United States
Sansum Clinic 540 W - USOR
🇺🇸Irving, Texas, United States
Texas Oncology Gulf Coast
🇺🇸Irving, Texas, United States
Texas Oncology West
🇺🇸Irving, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates, Sentara Health
🇺🇸Norfolk, Virginia, United States
Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Sunshine Coast University Private Hospital
🇦🇺Birtinya, Queensland, Australia
Box Hill Hospital
🇦🇺Melbourne, Victoria, Australia
Jewish General Hospital
🇨🇦Montreal, Canada
Peninsula and South Eastern Haematology and Oncology Group
🇦🇺Mount Waverly, Victoria, Australia
HPS Pharmacies - Adelaide
🇦🇺Adelaide, Australia
The Kinghorn Cancer Centre
🇦🇺Mt Kuring-gai, Australia
St John of God Hospital Subiaco
🇦🇺Subiaco, Australia
Ordensklinikum Barmherzige Schwestern
🇦🇹Linz, Austria
Klinikum Wels-Grieskirchen GmbH - Abteilung für Innere Medizin IV
🇦🇹Wels, Austria
Medizinische Universitat Wien
🇦🇹Wien, Austria
Institute Jules Bordet
🇧🇪Anderlecht, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
Grand Hôpital de Charleroi
🇧🇪Gilly, Belgium
CHU UCL Namur - Site Sainte-Elisabeth
🇧🇪Namur, Belgium
AZ Delta- Campus Rumbeke
🇧🇪Roeselare, Belgium
CHU de Québec Université Laval Hôpital du Saint Sacrement
🇨🇦Quebec, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Canada
BC Cancer-Vancouver Center
🇨🇦Vancouver, Canada
Institut Bergonie
🇫🇷Bordeaux Cedex, France
Centre François Baclesse
🇫🇷Caen, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Pharmacie Centre de Cancerologie de la Sarthe
🇫🇷Le Mans, France
Centre Oscar Lambret
🇫🇷Lille Cedex, France
AP HM Hopital de La Timone
🇫🇷Marseille, France
Pharmacie ICM Val d'Aurelle
🇫🇷Montpellier, France
Oncopôle Claudius Regaud Pharmacie
🇫🇷Toulouse, France
Gustave Roussy
🇫🇷Villejuif, France
Helios Klinikum Berlin Buch GmbH Klinik für Gynäkologie und Geburtshilfe
🇩🇪Berlin, Germany
Marienhospital Bottrop gGmbH
🇩🇪Dortmund, Germany
IRCCS Centro di Riferimento Oncologico di Aviano CRO
🇮🇹Aviano, Italy
Asst Papa Giovanni Xxiii
🇮🇹Bergamo, Italy
Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi Via Massarenti
🇮🇹Bologna, Italy
Ospedale San Raffaele S.r.l PPDS
🇮🇹Milano, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Italy
Istituto Oncologico Veneto - I.R.C.C.S.
🇮🇹Padova, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Chiba Cancer Center
🇯🇵Chiba-shi, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Japan
Osaka International Cancer Institute
🇯🇵Chuo-Ku, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka-shi, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Saitama Medical University International Medical Center
🇯🇵Hidaka-shi, Japan
Tokai University Hospital
🇯🇵Isesaki-shi, Japan
Sagara Hospital
🇯🇵Kagoshima-Shi, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Aichi Cancer Center
🇯🇵Nagoya-shi, Japan
Nagoya City University Hospital
🇯🇵Nagoya-shi, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
National Hospital Organization Osaka National Hospital
🇯🇵Osaka-Shi, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo-shi, Japan
Showa University Hospital
🇯🇵Tokyo, Japan
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Japan
Soon Chun Hyang University Cheonan Hospital
🇰🇷Cheonan-si, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Namdong-gu, Korea, Republic of
Gangnam Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Wojewódzki Szpital Specjalistyczny W Białej Podlaskiej
🇵🇱Biala Podlaska, Poland
Pratia MCM Kraków
🇵🇱Kraków, Poland
Pratia Poznan
🇵🇱Poznan, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Poznan, Poland
Hospital Universitario A Coruña
🇪🇸A Coruña, Spain
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Spain
Hospital Universitario Clinico San Cecilio
🇪🇸Granada, Spain
Hospital Beata Maria Ana
🇪🇸Madrid, Spain
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario de Canarias
🇪🇸San Cristóbal de La Laguna, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
CHUVI - H.U. Alvaro Cunqueiro
🇪🇸Vigo, Spain
Beatson West Of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom
Charring Cross Hospital
🇬🇧London, United Kingdom
The Christie - PPDS
🇬🇧Manchester, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom