Clinical trial NCT04466891: A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers
Official title: A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2-amplified Biliary Tract Cancers
Keywords: HER2
Bispecific antibody
Biparatopic antibody
Immunotherapy
Biliary Tract Cancer
Intra-hepatic cholangiocarcinoma
Extra-hepatic cholangiocarcinoma
Gallbladder cancer
JZP598
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: BeiGene
First posted: 2020-07-10
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single-arm, open-label, multi-cohort, multicenter study
Primary purpose: TREATMENT

Brief summary: This multicenter, open-label, single-arm trial will evaluate the anti-tumor activity of ZW25 (zanidatamab) monotherapy in subjects with human epidermal growth factor receptor 2 (HER2)-amplified, inoperable and advanced or metastatic biliary tract cancer (BTC), including intra-hepatic cholangiocarcinoma (ICC), extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).


Eligibility criteria: Inclusion Criteria:

* Histologically- or cytologically-confirmed BTC, including ICC, ECC or GBC.
* Locally advanced or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
* Received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who received gemcitabine in prior adjuvant or neoadjuvant treatment, if progression occurred \< 6 months from the latter of primary surgical resection or completion of gemcitabine-containing adjuvant therapy, they will be considered as having received 1 prior line of therapy for advanced disease.
* Subjects must test positive for HER2 amplification by ISH-assay at a central laboratory on a new biopsy or archival tissue. Note that fine needle aspirates (FNAs; cytology samples) and biopsies from sites of bone metastases are not acceptable. Testing may occur at any time after diagnosis of advanced or metastatic disease and before study enrollment.
* Male or female, ≥18 years of age (or the legal age of adulthood per country-specific regulations).
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
* Adequate organ function.
* Adequate cardiac function, as defined by left ventricular ejection fraction ≥ 50%.

Exclusion Criteria:

* Received systemic anti-cancer therapy within 3 weeks of the first dose of ZW25. Received radiotherapy within 2 weeks of the first dose of ZW25.
* Prior treatment with HER2-targeted agents.
* Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks at the time of screening).
* Known leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the investigator, the subject must be free of neurological symptoms of LMD.
* Concurrent uncontrolled or active hepatobiliary disorders or untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, unresolved biliary obstruction, infected biloma or abscess. Any complications must be resolved more than 2 weeks prior to the first dose of ZW25.
* Prior or concurrent malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen.
* Active hepatitis
* Infection with human immunodeficiency virus (HIV)-1 or HIV-2
* QTc Fridericia (QTcF) \> 470 ms.
* History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease.
* Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease.

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)
timeFrame: Up to 34 months
Secondary outcomes:
measure: Duration of Response (DOR) by ICR
timeFrame: Up to 34 months
measure: DOR at ≥ 16 Weeks by ICR
timeFrame: 24 weeks, up to 34 months
measure: Disease Control Rate (DCR) by ICR
timeFrame: Up to 34 months
measure: Progression-free Survival (PFS) by ICR
timeFrame: Up to 34 months
measure: ORR by Investigator Assessment
timeFrame: Up to 34 months
measure: DOR by Investigator Assessment
timeFrame: Up to 34 months
measure: DOR at ≥ 16 Weeks by Investigator Assessment
timeFrame: 24 weeks, up to 34 months
measure: DCR by Investigator Assessment
timeFrame: Up to 34 months
measure: PFS by Investigator Assessment
timeFrame: Up to 34 months
measure: Overall Survival
timeFrame: Up to 34 months
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 34 months
measure: Incidence of Laboratory Abnormalities
timeFrame: Up to 34 months
measure: Maximum Serum Concentration of ZW25
timeFrame: Up to 34 months
measure: Trough Concentration of ZW25
timeFrame: Up to 34 months
measure: Incidence of Anti-drug Antibodies (ADAs)
timeFrame: Up to 34 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Orlando
country: United States
facility: Advent Health Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center - Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Santiago
country: Chile
facility: Centro de Cáncer Nuestra Señora de la Esperanza
city: Temuco
country: Chile
facility: Radiomed (Clinica Alemana de Temuco)
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Affiliated Tumor Hospital of Harbin Medical University
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Huzhou
country: China
facility: Huzhou Central Hospital
city: Jinhua
country: China
facility: Jinhua Central Hospital
city: Lanzhou
country: China
facility: The First Hospital Of Lanzhou University
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
city: Shandong
country: China
facility: Shandong Provincial Third Hospital
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
city: Shanghai
country: China
facility: The Third Affiliated Hospital of the Chinese PLA
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Weifang
country: China
facility: Weifang People's Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Besançon
country: France
facility: Oncologie médicale Hopital Jean Minjoz
city: Brest
country: France
facility: Institut de Cancerologie et d'Hematologie Hopital Morvan - CHRU de Brest
city: Marseille
country: France
facility: Hopitaux de La Timone
city: Poitiers
country: France
facility: Département Oncologie Gastro-entérologie CHRU de Poitiers La Miletrie
city: Villejuif
country: France
facility: Département De Médecine
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia (IRCCS)
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - I.R.C.C.S.
city: Jinju-si
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang 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: Asan Medical Center Hospital
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: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Universitario Germans Trias i Pujol
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Doce de Octubre
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: London
country: United Kingdom
facility: University College London Hospitals (UCLH)
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
References: