A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers
- Conditions
- HER2-amplified Biliary Tract Cancers
- Interventions
- Drug: ZW25 (Zanidatamab)
- Registration Number
- NCT04466891
- Lead Sponsor
- Jazz Pharmaceuticals
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 87
- 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%.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ZW25 (Zanidatamab) Monotherapy ZW25 (Zanidatamab) -
- Primary Outcome Measures
Name Time Method Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR) Up to 34 months Number of participants who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is defined as a disappearance of all target and non-target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of all target lesions.
- Secondary Outcome Measures
Name Time Method PFS by Investigator Assessment Up to 34 months The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), or death from any cause
DOR at ≥ 16 Weeks by ICR 24 weeks, up to 34 months Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
DOR at ≥ 16 Weeks by Investigator Assessment 24 weeks, up to 34 months Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
ORR by Investigator Assessment Up to 34 months Number of subjects who achieved a confirmed BOR of either CR or PR during treatment per RECIST 1.1
DOR by Investigator Assessment Up to 34 months The time from the first confirmed objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, or death from any cause
Overall Survival Up to 34 months The time from the first dose of study treatment until the date of death from any cause
Maximum Serum Concentration of ZW25 Up to 34 months Trough Concentration of ZW25 Up to 34 months Minimum observed serum concentration (trough)
Disease Control Rate (DCR) by ICR Up to 34 months Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1
DCR by Investigator Assessment Up to 34 months Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1
Duration of Response (DOR) by ICR Up to 34 months The time from the first confirmed objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, or death from any cause
Progression-free Survival (PFS) by ICR Up to 34 months The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), or death from any cause
Incidence of Adverse Events (AEs) Up to 34 months Number of subjects who experienced AEs or serious adverse events
Incidence of Laboratory Abnormalities Up to 34 months Number of subjects who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
Incidence of Anti-drug Antibodies (ADAs) Up to 34 months Number of subjects who develop ADAs
Trial Locations
- Locations (67)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of California Los Angeles
🇺🇸Santa Monica, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Advent Health Cancer Institute
🇺🇸Orlando, Florida, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Scroll for more (57 remaining)Banner MD Anderson Cancer Center🇺🇸Gilbert, Arizona, United States