Clinical trial NCT06282575: Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer
Official title: An Open-label Randomized Trial of the Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy Alone for Advanced HER2-positive Biliary Tract Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Biliary Tract Cancer
Keywords: JZP598
ZW25
HER-2 positive BIliary Tract cancer
Gallbladder Cancer
Intrahepatic Cholangiocarcinoma (ICC)
Extrahepatic Cholangiocarcinoma (ECC)
Zanidatamab
HER-2 overexpression
HER-2 amplification
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 286
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 purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.


Eligibility criteria: Inclusion Criteria

1. Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
2. Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
3. Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
4. HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
5. Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
6. Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Adequate organ function
9. Females of childbearing potential must have a negative pregnancy test result.
10. Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.

Exclusion Criteria

1. Prior treatment with a HER2-targeted agent
2. Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
3. The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
4. Use of systemic corticosteroids.
5. Brain metastases
6. Severe chronic or active infections
7. History of allogeneic organ transplantation.
8. Active or prior autoimmune inflammatory conditions
9. History of interstitial lung disease or non-infectious pneumonitis.
10. Participation in another clinical trial with an investigational medicinal product within the last 3 months.
11. Females who are breastfeeding
12. Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
13. Use of phenytoin

Primary outcomes:
measure: Progression Free Survival (PFS) in participants with Immunohistochemistry (IHC) 3+ tumors
timeFrame: Up to 52 months
Secondary outcomes:
measure: Overall survival (OS) in participants with IHC 3+ tumors
timeFrame: Up to 68 months
measure: Progression Free Survival for all participants
timeFrame: Up to 68 months
measure: OS for all participants
timeFrame: Up to 68 months
measure: Number of participants achieving Confirmed objective response rate (cORR)
timeFrame: Up to 68 months
measure: Duration of response (DOR)
timeFrame: Up to 68 months
measure: Number of Patients reporting Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to 68 months
measure: Maximum serum concentration of Zanidatamab
timeFrame: Up to 68 months
measure: Number of participants who develop Anti-drug antibodies (ADAs) to Zanidatamab
timeFrame: Up to 68 months
measure: Time to definitive deterioration (TDD) for participants with IHC 3+ tumors in patient-reported Physical Functioning (PF) domain score as measured by the EORTC QLQ-C30
timeFrame: Up to 68 months
measure: TDD for all participants in patient-reported PF domain score as measured by the EORTC QLQ-C30
timeFrame: Up to 68 months
measure: TDD for participants with IHC 3+ tumors in patient-reported symptoms scores as measured by the EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain and Pruritis)
timeFrame: Up to 68 months
measure: TDD for all participants in patient-reported symptoms scores as measured by the EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain, and Pruritis)
timeFrame: Up to 68 months
Other outcomes:
Locations:
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Orlando
country: United States
facility: AdventHealth Hematology and Oncology
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Westwood
country: United States
facility: The University of Kansas Cancer Center - Westwood
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute - Audubon
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Maple Grove
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Morristown
country: United States
facility: Atlantic Health System/Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone - Ambulatory Care Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Centers
state: New York
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - DFW
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The Univerrsity of Texas MD Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University, VCU Health
state: Virginia
city: Ciudad Autónoma de Buenos Aires (CABA)
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Buenos Altes
city: San Salvador De Jujuy
country: Argentina
facility: Fundación ARS Médica
state: Jujuy
city: Viedma
country: Argentina
facility: Centro de Investigaciónes Clínicas - Clínica Viedma
state: Río Negro
city: Rosario
country: Argentina
facility: Hospital Provincial Del Centenario
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto Médico de la Fundación Estudios Clínicos
state: Santa Fe
city: San Miguel De Tucumán
country: Argentina
facility: CAIPO Centro para la Atención Integral del Paciente Oncológico
state: Tucumán
city: San Miguel De Tucumán
country: Argentina
facility: Centro Médico en Oncología Clínica EXELSUS S.R.L
state: Tucumán
city: Córdoba
country: Argentina
facility: Centro Médico Privado CEMAIC
city: Bonheiden
country: Belgium
facility: Imelda VZW
state: Antwerpen
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
state: Rio Grande Do Norte
city: Porto Alegrev
country: Brazil
facility: Irmandade Da Santa Casa de Misericordia de Porto Alegre - ISCMPA
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Fundação Pio XII Hospital de Amor de Barretos
state: São Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto (FUNFARME)
state: São Paulo
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora Da Conceição/Centro Integrado de Pesquisa em Oncologia CIPO-GHC
city: LondonO
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre - University Health Network
state: Ontario
city: Temuco
country: Chile
facility: James Lind Centro de Investigacion del Cancer
state: Araucanía
city: Rancagua
country: Chile
facility: Servicios Médicos URUMED SpA
state: Libertador Gen Bernardo O Higgins
city: Puerto Montt
country: Chile
facility: Clinica Puerto Montt
state: Los Lagos
city: Santiago
country: Chile
facility: Fundación Arturo López Pérez (FALP)
state: Metropolitana
city: Santiago
country: Chile
facility: Oncovida
state: Metropolitana
city: Santiago
country: Chile
facility: Hospital Clinico Universidad de Chile
state: Region Metropolitana
city: Santiago
country: Chile
facility: Centro de Investigacion y Especialidades Medicas (CDIEM)
state: Región-Metropolitana
city: Santiago
country: Chile
facility: Biocinetic Ltda
state: Región-Metropolitana
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno, Interní hematologická a onkologická klinika
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove, Klinika onkologie a radioterapie
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole, Onkologicka klinika
city: Helsinki
country: Finland
facility: Docrates Cancer Center
city: Helsinki
country: Finland
facility: Comprehensive Cancer Center, Helsinki University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Toulouse
country: France
facility: CHU de Toulouse- (Toulouse University Hospital Center)
state: Cedex 9
city: Besançon
country: France
facility: CHU Besancon
state: Cedex
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut Leveque
state: Cedex
city: Brest
country: France
facility: CHU Brest Hôpital de la Cavale Blanche
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Clichy
country: France
facility: Hospital Beaujon University
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Montpellier
country: France
facility: CHU Montepellier - Hôpital Saint Eloi
city: Poitiers
country: France
facility: CHU Poitiers
city: Saint-Herblain Cedex
country: France
facility: Institut de Cancérologie de l'Ouest
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen - Medizinische Universitätsklinik, Innere Medizin I
state: Baden-Wuttemberg
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
state: Baden-Württemberg
city: München
country: Germany
facility: LMU Universitätsklinikum München, Campus Großhadern, Medizinische Klinik und Poliklinik III - Hämatologie und Onkologie
state: Bayern
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest - Institut für Klinisch-Onkologische Forschung (IFK)
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover - Klinik Fur Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie
state: Nieder-Sachsen
city: Lubeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Lübeck, Medizinische Klinik I (MKI)
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin - Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hamatologie und Tumorimmunologie
city: Hamburg
country: Germany
facility: Asklepios Tumorzentrum Hamburg, Asklepios Klinik Altona - Onkologie und Palliativmedizin mit Sektionen Hamatologie und Rheumatologie
city: Belagavi
country: India
facility: KLES Dr Prabhakar Kore Hospital and Medical Research Centre
state: Karnataka
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
city: Nashik
country: India
facility: Chopda Medicare & Research Centre Pvt. Ltd - Magnum Heart Institute
state: Maharashtra
city: Hyderabad
country: India
facility: AIG Hospitals (A Unit of Asian Institute of Gastroenterology)
state: Telangana
city: Hyderabad
country: India
facility: Pi Health Cancer Hospital
state: Telangana
city: Varanasi
country: India
facility: Mahamana Pandit Madan Mohan Malviya Cancer Centre
state: Uttar Pradesh
city: New Delhi
country: India
facility: Max Super Speciality Hospital - Saket (a unit of Devki Devi foundation)
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Institute And Research Centre
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: The Hadassah University Medical Center, Ein Kerem Hospital
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center, Bellinson Hospital
city: Ramat Gan, HaMerkaz
country: Israel
facility: The Chaim Sheba Medical Center, Tel Hashomer
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center (Ichilov)
city: Monserrato
country: Italy
facility: Azienda Ospedaliero Universitaria di Cagliari Presidio Ospedaliero Duilio Casula
state: Cagliari
city: Candiolo
country: Italy
facility: Instituo di Candiolo, Fondazione del Piemonte per l'Oncologia (IRCCS)
state: Torino
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale per lo studio e la cura dei Tumori
city: Napoli
country: Italy
facility: AOU dell'Universit~ degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: Veneto Institute of Oncology IOV - I.R.C.C.S.
city: Pisa
country: Italy
facility: Azienda Ospedaliero - Universitaria Pisana
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale - P.O. S. Maria della Misericordia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Chiba-shi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama-Shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
state: Fukuoka
city: Sapporo-Shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaidô
city: Kanazawa-shi
country: Japan
facility: Kanazawa University Hospital
state: Isikawa
city: Kagoshima-shi
country: Japan
facility: Kagoshima University Hospital
state: Kagoshima
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Kyoto City
country: Japan
facility: Kyoto University Hospital
state: Kyôto
city: Tsu-Shi
country: Japan
facility: Mie University Hospital
state: Mie
city: Sendai-Shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Niigata-shi
country: Japan
facility: Niigata University Medical and Dental Hospital
state: Niigata
city: Osaka-shi
country: Japan
facility: Osaka Prefectural Hospital Organization Osaka International Cancer Institute
state: Osaka
city: Bunkyo-ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation For Cancer Research
state: Tokyo
city: Mitaka-shi
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Ube-Shi
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Suita-Shi
country: Japan
facility: Osaka University Hospital
state: Ôsaka
city: Bundang-Gu, Seongnam-Si
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
state: Gyeonggi-do
city: Ilsandong-gu, Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Almada
country: Portugal
facility: Unidade Local de Saude de Almada-Seixal, E.P.E. - Hospital Garcia de Orta
city: Coimbra
country: Portugal
facility: Unidade Local de Saude de Coimbra, EPE - Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Unidade Local de Saúde de São José - Hospital de Santo António dos Capuchos
city: Lisboa
country: Portugal
facility: Champalimaud Clinical Center
city: Porto
country: Portugal
facility: Instituto Português de Oncologia Do Porto Francisco Gentil, EPE
city: Rio Piedras
country: Puerto Rico
facility: Hospital Oncologico, Puerto Rico Medical Center
city: Oradea
country: Romania
facility: Spital Clinic Judetean de Urgenta Bihor
state: Bihor
city: Craiova
country: Romania
facility: Centrul De Oncologie "SF. Nectarie" S.R.L.
state: Dolj
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Iasi
country: Romania
facility: Centrul de Oncologie Euroclinic SRL
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia, Clinic for Gastroenterohepatology
city: Belgrade
country: Serbia
facility: Military Medical Academy, Clinic for Gastroenterology and Hepatology
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute of Vojvodina, Internal Oncology Clinic
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago -Hospital Clinico Universitario de Santiago
state: A Coruna
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology/Hospital Universitari de Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Göteborg
country: Sweden
facility: Onkologiska mottagningen, Sahlgrenska Universitetssjukhuset
city: Huddinge
country: Sweden
facility: Cancerstudieenheten Huddinge, Karolinska Universitetssjukhuset Huddinge
city: Malmö
country: Sweden
facility: Onkologiska mottagningen, Skånes Universitetssjukhus Malmö
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University - Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital Kaohsiung Branch of the Chang Gung Medical Foundation
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkou Branch of the Chang Gung Medical Foundation
city: Ankara
country: Turkey
facility: Hacettepe University Cancer Institute
state: Sihhiye
city: Edirne
country: Turkey
facility: Trakya University Faculty of Medicine
city: London
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: England
city: London
country: United Kingdom
facility: NHS Foundation Trust Royal Marsden Hospital
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
city: Surrey
country: United Kingdom
facility: Royal Marsden Hospital NHS Foundation Trust
state: England
city: Edinburgh
country: United Kingdom
facility: Western General Hospital, Edinburgh Cancer Centre
state: Scotland
Study officials:
References: