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A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04466891
Recruitment Status : Recruiting
First Posted : July 10, 2020
Last Update Posted : November 10, 2020
Sponsor:
Collaborator:
BeiGene, Ltd.
Information provided by (Responsible Party):
Zymeworks Inc.

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).

Condition or disease Intervention/treatment Phase
HER2-amplified Biliary Tract Cancers Drug: ZW25 (Zanidatamab) Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: single-arm, open-label, multi-cohort, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers
Actual Study Start Date : October 1, 2020
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: ZW25 (Zanidatamab) Monotherapy Drug: ZW25 (Zanidatamab)
Administered intravenously

Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay
Subjects will be tested for HER2 gene-amplification using the ISH-based companion diagnostic assay

Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay
Subjects will be tested for HER2 protein-expression using the IHC-based companion diagnostic assay




Primary Outcome Measures :
  1. Confirmed objective response rate (ORR) by independent central review (ICR) [ Time Frame: Up to 2.5 years ]
    Number of subjects 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


Secondary Outcome Measures :
  1. Duration of response (DOR) by ICR [ Time Frame: Up to 2.5 years ]
    The time from the first objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, clinical progression, or death from any cause

  2. DOR at ≥ 16 weeks by ICR [ Time Frame: 24 weeks to 2.5 years ]
    Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1

  3. Disease control rate (DCR) by ICR [ Time Frame: Up to 2.5 years ]
    Number of subjects who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1

  4. Progression-free survival (PFS) by ICR [ Time Frame: Up to 2.5 years ]
    The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause

  5. ORR by investigator assessment [ Time Frame: Up to 2.5 years ]
    Number of subjects who achieved a BOR of either CR or PR during treatment per RECIST 1.1

  6. DOR by investigator assessment [ Time Frame: Up to 2.5 years ]
    The time from the first objective response (CR or PR) to documented PD per RECIST 1.1, clinical progression, or death from any cause

  7. DOR at ≥ 16 weeks by investigator assessment [ Time Frame: 24 weeks to 2.5 years ]
    Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1

  8. DCR by investigator assessment [ Time Frame: Up to 2.5 years ]
    Number of subjects who achieved a best response of CR, PR, or SD during treatment per RECIST 1.1

  9. PFS by investigator assessment [ Time Frame: Up to 2.5 years ]
    The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause

  10. Overall survival [ Time Frame: Up to 2.5 years ]
    The time from the first dose of study treatment until the date of death from any cause

  11. Incidence of adverse events (AEs) [ Time Frame: Up to 2.5 years ]
    Number of subjects who experienced AEs or serious adverse events

  12. Incidence of laboratory abnormalities [ Time Frame: Up to 2.5 years ]
    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

  13. Maximum serum concentration of ZW25 [ Time Frame: Up to 2.5 years ]
  14. Trough concentration of ZW25 [ Time Frame: Up to 2.5 years ]
    Minimum observed serum concentration (trough)

  15. Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 2.5 years ]
    Number of subjects who develop ADAs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 regimen of systemic therapy for advanced disease, including 1 gemcitabine-containing regimen, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who have received prior adjuvant or neoadjuvant treatment, if progression has occurred < 6 months from completion of the adjuvant or neoadjuvant therapy, this regimen will be considered as 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, biloma or abscess. Any complications should be resolved within 2 weeks prior to the first dose of ZW25.
  • Prior or concurrent invasive 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04466891


Contacts
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Contact: Zymeworks Clinical Trial Resource (206) 237-1030 medinfo@zymeworks.com

Locations
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United States, California
University of California Los Angeles Recruiting
Santa Monica, California, United States, 90404
Principal Investigator: Saeed Sadeghi, MD         
The Oncology Institute of Hope and Innovation Recruiting
Whittier, California, United States, 90603
Principal Investigator: Omkar Marathe, MD         
United States, Florida
Advent Health Cancer Institute Recruiting
Orlando, Florida, United States, 32804
Principal Investigator: Mohamedtaki Tejani, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Principal Investigator: Benjamin Tan, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: James Harding, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Shubham Pant, MD         
Korea, Republic of
Seoul National University Bundang Hospital Recruiting
Seongnam, Korea, Republic of, 13620
Principal Investigator: Jin Won Kim, MD         
Severance Hospital Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 03722
Principal Investigator: Choong-Kun Lee, MD         
Asan Medical Center Hospital Recruiting
Seoul, Korea, Republic of, 05505
Principal Investigator: Heung Moon Chang, MD         
Spain
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Principal Investigator: Teresa Macarulla Mercade, MD         
Hospital Universitario Reina Sofia Recruiting
Cordoba, Spain, 14004
Principal Investigator: Rosa Rodriguez Alonso, MD         
Hospital Universitario Doce de Octubre Recruiting
Madrid, Spain, 28041
Principal Investigator: Jorge Adeva Alfonso, MD         
Hospital Universitario HM Sanchinarro - CIOCC (Centro Integral Oncologíco Clara Campal) Recruiting
Madrid, Spain, 28050
Principal Investigator: Antonio Cubillo Gracián, MD         
Hospital Universitari Parc Tauli de Sabadell Recruiting
Sabadell, Spain, 08208
Principal Investigator: Paula Ribera Fernandez, MD         
Hospital Miguel Servet Recruiting
Zaragoza, Spain, 50009
Principal Investigator: Roberto Pazo Cid, MD         
Sponsors and Collaborators
Zymeworks Inc.
BeiGene, Ltd.
Investigators
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Study Director: Neil Josephson, MD Zymeworks Inc.
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Responsible Party: Zymeworks Inc.
ClinicalTrials.gov Identifier: NCT04466891    
Other Study ID Numbers: ZWI-ZW25-203
2020-000459-11 ( EudraCT Number )
First Posted: July 10, 2020    Key Record Dates
Last Update Posted: November 10, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Zymeworks Inc.:
HER2
Bispecific antibody
Biparatopic antibody
Immunotherapy
Biliary Tract Cancer
Intra-hepatic cholangiocarcinoma
Extra-hepatic cholangiocarcinoma
Gallbladder cancer
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases