Clinical Trials /

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

NCT04466891

Description:

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).

Related Conditions:
  • Biliary Tract Carcinoma
  • Extrahepatic Cholangiocarcinoma
  • Gallbladder Carcinoma
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: ZWI-ZW25-203
  • SECONDARY ID: 2020-000459-11
  • NCT ID: NCT04466891

Conditions

  • HER2-amplified Biliary Tract Cancers

Interventions

DrugSynonymsArms
ZW25 (Zanidatamab)ZW25 (Zanidatamab) Monotherapy

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
ZW25 (Zanidatamab) MonotherapyExperimental
  • ZW25 (Zanidatamab)

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed objective response rate (ORR) by independent central review (ICR)
Time Frame:Up to 2.5 years
Safety Issue:
Description: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

Measure:Duration of response (DOR) by ICR
Time Frame:Up to 2.5 years
Safety Issue:
Description: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
Measure:DOR at ≥ 16 weeks by ICR
Time Frame:24 weeks to 2.5 years
Safety Issue:
Description:Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
Measure:Disease control rate (DCR) by ICR
Time Frame:Up to 2.5 years
Safety Issue:
Description:Number of subjects who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1
Measure:Progression-free survival (PFS) by ICR
Time Frame:Up to 2.5 years
Safety Issue:
Description: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
Measure:ORR by investigator assessment
Time Frame:Up to 2.5 years
Safety Issue:
Description:Number of subjects who achieved a BOR of either CR or PR during treatment per RECIST 1.1
Measure:DOR by investigator assessment
Time Frame:Up to 2.5 years
Safety Issue:
Description:The time from the first objective response (CR or PR) to documented PD per RECIST 1.1, clinical progression, or death from any cause
Measure:DOR at ≥ 16 weeks by investigator assessment
Time Frame:24 weeks to 2.5 years
Safety Issue:
Description:Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
Measure:DCR by investigator assessment
Time Frame:Up to 2.5 years
Safety Issue:
Description:Number of subjects who achieved a best response of CR, PR, or SD during treatment per RECIST 1.1
Measure:PFS by investigator assessment
Time Frame:Up to 2.5 years
Safety Issue:
Description: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
Measure:Overall survival
Time Frame:Up to 2.5 years
Safety Issue:
Description:The time from the first dose of study treatment until the date of death from any cause
Measure:Incidence of adverse events (AEs)
Time Frame:Up to 2.5 years
Safety Issue:
Description:Number of subjects who experienced AEs or serious adverse events
Measure:Incidence of laboratory abnormalities
Time Frame:Up to 2.5 years
Safety Issue:
Description: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
Measure:Maximum serum concentration of ZW25
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:Trough concentration of ZW25
Time Frame:Up to 2.5 years
Safety Issue:
Description:Minimum observed serum concentration (trough)
Measure:Incidence of anti-drug antibodies (ADAs)
Time Frame:Up to 2.5 years
Safety Issue:
Description:Number of subjects who develop ADAs

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Zymeworks Inc.

Trial Keywords

  • HER2
  • Bispecific antibody
  • Biparatopic antibody
  • Immunotherapy
  • Biliary Tract Cancer
  • Intra-hepatic cholangiocarcinoma
  • Extra-hepatic cholangiocarcinoma
  • Gallbladder cancer

Last Updated

July 6, 2020