A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers (HERIZON-BTC-01)

• ClinicalTrials.gov Identifier: NCT04466891
• Recruitment Status: Active, not recruiting
• First Posted: July 10, 2020
• Last Update Posted: February 1, 2023
• Sponsor: Zymeworks Inc.
• Collaborator: BeiGene, Ltd.
• Information provided by (Responsible Party): Zymeworks Inc.

Tracking Information

• First Submitted Date: July 6, 2020
• First Posted Date: July 10, 2020
• Last Update Posted Date: February 1, 2023
• Actual Study Start Date: October 1, 2020
• Actual Primary Completion Date: October 10, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 6, 2020)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Incidence of adverse events (AEs) [ Time Frame: Up to 2.5 years ]
  Number of subjects who experienced AEs or serious adverse events
• 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
• Maximum serum concentration of ZW25 [ Time Frame: Up to 2.5 years ]
• Trough concentration of ZW25 [ Time Frame: Up to 2.5 years ]
  Minimum observed serum concentration (trough)
• Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 2.5 years ]
  Number of subjects who develop ADAs

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: HER2-amplified Biliary Tract Cancers

Intervention

• 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

Study Arms

Experimental: ZW25 (Zanidatamab) Monotherapy

Interventions:

• Drug: ZW25 (Zanidatamab)
• Diagnostic Test: In situ hybridization (ISH)-based companion diagnostic assay
• Diagnostic Test: Immunohistochemistry (IHC)-based companion diagnostic assay

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 30, 2023): 87
• Original Estimated Enrollment (submitted: July 6, 2020): 100
• Estimated Study Completion Date: June 2024
• Actual Primary Completion Date: October 10, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Chile, China, France, Italy, Korea, Republic of, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04466891
• Other Study ID Numbers: ZWI-ZW25-203; 2020-000459-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Zymeworks Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Zymeworks Inc.
• Original Study Sponsor: Same as current
• Collaborators: BeiGene, Ltd.

Investigators

• Study Director: Phillip Garfin, MD, PhD; Zymeworks Inc.
• Study Director: Jiafang Ma, MD; BeiGene, Ltd.

• PRS Account: Zymeworks Inc.
• Verification Date: January 2023