Clinical trial NCT06435429: 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
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic HER2-positive Breast Cancer
Keywords: Zanidatamab
Trastuzumab
Metastatic HER2-positive breast cancer
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-05-30
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Progression-free Survival (PFS) Per RECIST Version 1.1 As Assessed by Blinded Independent Central Review (BICR)
timeFrame: Until disease progression or death, up to approximately 44 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Until death, up to approximately 80 months
measure: Confirmed Objective Response Rate (ORR) Per RECIST Version 1.1, As Assessed by BICR
timeFrame: Until disease progression or death, up to approximately 44 months
measure: Duration of Response (DOR) Per RECIST Version 1.1, As Assessed by BICR
timeFrame: Until disease progression or death, up to approximately 44 months
measure: PFS Per RECIST Version 1.1, As Assessed By Investigator
timeFrame: Until disease progression or death, up to approximately 44 months
measure: Confirmed ORR Per RECIST Version 1.1, As Assessed By Investigator
timeFrame: Until disease progression or death, up to approximately 44 months
measure: DOR Per RECIST Version 1.1, As Assessed By Investigator
timeFrame: Until disease progression or death, up to approximately 44 months
measure: Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events As Graded by NCI CTCAE Version 5.0
timeFrame: Up to approximately 44 months
measure: Number of Participants With Dose Reductions
timeFrame: Up to approximately 44 months
measure: Number of Participants Discontinuing Study Treatment Due to TEAEs
timeFrame: Up to approximately 44 months
measure: Serum Concentrations of Zanidatamab
timeFrame: Up to approximately 44 months
measure: Number of Participants Positive for Anti-drug Antibodies to Zanidatamab
timeFrame: Up to approximately 44 months
measure: 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
timeFrame: Up to approximately 44 months
measure: 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)
timeFrame: Up to approximately 44 months
measure: 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)
timeFrame: Up to approximately 44 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Tucson - Wilmot
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Cerritos
country: United States
facility: The Oncology Institute Of Hope And Innovation
state: California
city: Los Angeles
country: United States
facility: USC-Norris Comprehensive Cancer Center - Investigational Drug Service IDS
state: California
city: Aurora
country: United States
facility: University of Colorado-Cancer Center-PPDS
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Washington Cancer Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Research South
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists Research North
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists Research East
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Coon Rapids
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Hackensack
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Long Island City
country: United States
facility: Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center 160 E 34th St
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center 161 Fort Washington
state: New York
city: Asheville
country: United States
facility: Messino Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care (OHC)
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center 11100 Euclid Ave
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of The University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth
state: Texas
city: Houston
country: United States
facility: U.T. MD Anderson Cancer Center, Investigational Pharmacy Services
state: Texas
city: Houston
country: United States
facility: Millennium Research and Clinical Development
state: Texas
city: Irving
country: United States
facility: Maryland Oncology Hematology Healing Way - USOR
state: Texas
city: Irving
country: United States
facility: Medical Oncology Hematology Consultants
state: Texas
city: Irving
country: United States
facility: Nexus Health
state: Texas
city: Irving
country: United States
facility: Sansum Clinic 540 W - USOR
state: Texas
city: Irving
country: United States
facility: Texas Oncology Gulf Coast
state: Texas
city: Irving
country: United States
facility: Texas Oncology West
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates, Sentara Health
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Birtinya
country: Australia
facility: Sunshine Coast University Private Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Mount Waverly
country: Australia
facility: Peninsula and South Eastern Haematology and Oncology Group
state: Victoria
city: Adelaide
country: Australia
facility: HPS Pharmacies - Adelaide
city: Mt Kuring-gai
country: Australia
facility: The Kinghorn Cancer Centre
city: Subiaco
country: Australia
facility: St John of God Hospital Subiaco
city: Linz
country: Austria
facility: Ordensklinikum Barmherzige Schwestern
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH - Abteilung für Innere Medizin IV
city: Wien
country: Austria
facility: Medizinische Universitat Wien
city: Anderlecht
country: Belgium
facility: Institute Jules Bordet
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gilly
country: Belgium
facility: Grand Hôpital de Charleroi
city: Namur
country: Belgium
facility: CHU UCL Namur - Site Sainte-Elisabeth
city: Roeselare
country: Belgium
facility: AZ Delta- Campus Rumbeke
city: Brasilia
country: Brazil
facility: DASA Hospital Brasilia
city: Ceara
country: Brazil
facility: Centro Regional Integrado de Oncologia
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul PUCRS
city: Recife
country: Brazil
facility: Real Hospital Portugues de Beneficiencia Em Pernambuco
city: Salvador
country: Brazil
facility: Nucleo de Oncologia Da Bahia
city: São Caetano do Sul
country: Brazil
facility: Ceon Pesquisas Ltda
city: Montreal
country: Canada
facility: Jewish General Hospital
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
city: Quebec
country: Canada
facility: CHU de Québec Université Laval Hôpital du Saint Sacrement
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
city: Vancouver
country: Canada
facility: BC Cancer-Vancouver Center
city: Bordeaux Cedex
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre François Baclesse
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Le Mans
country: France
facility: Pharmacie Centre de Cancerologie de la Sarthe
city: Lille Cedex
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: AP HM Hopital de La Timone
city: Montpellier
country: France
facility: Pharmacie ICM Val d'Aurelle
city: Strasbourg
country: France
facility: ICANS - Institut de cancérologie Strasbourg Europe
city: Toulouse
country: France
facility: Oncopôle Claudius Regaud Pharmacie
city: Villejuif
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Helios Klinikum Berlin Buch GmbH Klinik für Gynäkologie und Geburtshilfe
city: Dortmund
country: Germany
facility: Marienhospital Bottrop gGmbH
city: Athens
country: Greece
facility: Aretaieio Hospital
city: Athens
country: Greece
facility: Athens Medical Center
city: Patra
country: Greece
facility: University General Hospital of Patras
city: Thessaloniki
country: Greece
facility: European Interbalkan Medical Center
city: Aviano
country: Italy
facility: IRCCS Centro di Riferimento Oncologico di Aviano CRO
city: Bergamo
country: Italy
facility: Asst Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi Via Massarenti
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l PPDS
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - I.R.C.C.S.
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Chiba-shi
country: Japan
facility: Chiba Cancer Center
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Chuo-Ku
country: Japan
facility: Osaka International Cancer Institute
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
city: Isesaki-shi
country: Japan
facility: Tokai University Hospital
city: Kagoshima-Shi
country: Japan
facility: Sagara Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
city: Nagoya-shi
country: Japan
facility: Nagoya City University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka-Shi
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Sapporo-shi
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
city: Tokyo
country: Japan
facility: Showa University Hospital
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
city: Cheonan-si
country: Korea, Republic of
facility: Soon Chun Hyang University Cheonan Hospital
city: Namdong-gu
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Biala Podlaska
country: Poland
facility: Wojewódzki Szpital Specjalistyczny W Białej Podlaskiej
city: Bialystok
country: Poland
facility: Białostockie Centrum Onkologii im. Marii Skłodowskiej-Curie w Białymstoku
city: Kraków
country: Poland
facility: Pratia MCM Kraków
city: Poznan
country: Poland
facility: Pratia Poznan
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy w Warszawie
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: ICO Badalona-H.U. Germans Trias i Pujol
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Granada
country: Spain
facility: Hospital Universitario Clinico San Cecilio
city: Madrid
country: Spain
facility: Hospital Beata Maria Ana
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: San Cristóbal de La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Vigo
country: Spain
facility: CHUVI - H.U. Alvaro Cunqueiro
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West Of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Charring Cross Hospital
city: Manchester
country: United Kingdom
facility: The Christie - PPDS
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
References: