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).
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
Drug | Synonyms | Arms |
---|
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
Name | Type | Description | Interventions |
---|
ZW25 (Zanidatamab) Monotherapy | Experimental | | |
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.
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
August 17, 2021