Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

An Open-label Randomized Trial of the Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy Alone for Advanced HER2-positive Biliary Tract Cancer

The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Cancer; HER2 Gene Mutation
• Intervention / Treatment: Drug: Zanidatamab; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pembrolizumab; Drug: Durvalumab

• Study Type: Interventional
• Enrollment (Estimated): 286
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure & Transparency; Phone Number: 215-832-3750; Email: ClinicalTrialDisclosure@JazzPharma.com

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Recruiting
    • Hospital Oncologico, Puerto Rico Medical Center
• United States
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Recruiting
      • Rocky Mountain Cancer Centers, LLP
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Not yet recruiting
      • Norton Cancer Institute - Audubon
  • Minnesota
    • Maple Grove, Minnesota, United States, 55369
      • Recruiting
      • Minnesota Oncology Hematology, P.A.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology - DFW

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC)..
2. Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
3. Received no more than 2 cycles of systemic therapy with gemcitabine and a platinum agent with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
4. HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
5. Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
6. Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Adequate organ function
9. Females of childbearing potential must have a negative pregnancy test result.
10. Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.

Exclusion Criteria

1. Prior treatment with a HER2-targeted agent
2. Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
3. The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
4. Use of systemic corticosteroids.
5. Brain metastases
6. Severe chronic or active infections
7. History of allogeneic organ transplantation.
8. Active or prior autoimmune inflammatory conditions
9. History of interstitial lung disease or non-infectious pneumonitis.
10. Participation in another clinical trial with an investigational medicinal product within the last 3 months.
11. Females who are breastfeeding
12. Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanidatamab with Standard-of-care Therapy Arm; Zanidatamab plus standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.	Drug: Zanidatamab; Administered intravenously (IV); Other Names: ZW25; JZP598; Drug: Cisplatin; Administered intravenously (IV); Drug: Gemcitabine; Administered intravenously (IV); Drug: Pembrolizumab; Administered intravenously (IV); Drug: Durvalumab; Administered intravenously (IV)
Active Comparator: Standard-of-care Therapy Arm; Standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.	Drug: Cisplatin; Administered intravenously (IV); Drug: Gemcitabine; Administered intravenously (IV); Drug: Pembrolizumab; Administered intravenously (IV); Drug: Durvalumab; Administered intravenously (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) in participants with Immunohistochemistry (IHC) 3+ tumors	PFS is defined as the time from the date of randomization to the date of documented disease progression, or death from any cause.	Up to 52 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS) in participants with IHC 3+ tumors	OS is defined as the time from randomization to death, due to any cause.	Up to 68 months
Progression Free Survival for all participants	PFS is defined as the time from the date of randomization to the date of documented disease progression, or death from any cause.	Up to 68 months
OS for all participants	OS is defined as the time from randomization to death, due to any cause.	Up to 68 months
Number of participants achieving Confirmed objective response rate (cORR)	Confirmed objective response rate is defined as achieving a confirmed best overall response of Complete Response (CR) or Partial Response (PR)	Up to 68 months
Duration of response (DOR)	Duration of response is defined as the time from the first objective response (CR or PR) to documented Progressive Disease (PD) or death, from any cause.	Up to 68 months
Number of Patients reporting Treatment-Emergent Adverse Events (TEAE)		Up to 68 months
Maximum serum concentration of Zanidatamab		Up to 68 months
Number of participants who develop Anti-drug antibodies (ADAs) to Zanidatamab		Up to 68 months
Time to definitive deterioration (TDD) for participants with IHC 3+ tumors in patient-reported Physical Functioning (PF) domain score as measured by the EORTC QLQ-C30	TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) final scores range from 0 to 100, where higher scores reflect better functioning	Up to 68 months
TDD for all participants in patient-reported PF domain score as measured by the EORTC QLQ-C30	TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC QLQ-C30 final scores range from 0 to 100, where higher scores reflect better functioning.	Up to 68 months
TDD for participants with IHC 3+ tumors in patient-reported symptoms scores as measured by the EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain and Pruritis)	TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer module (QLQ-BIL21) (Pain, Jaundice, Abdominal Pain, and Pruritis) final scores range from 0 to 100, where higher scores reflect better functioning.	Up to 68 months
TDD for all participants in patient-reported symptoms scores as measured by the EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain, and Pruritis)	TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain, and Pruritis) final scores range from 0 to 100, where higher scores reflect better functioning.	Up to 68 months

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: February 21, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Gallbladder Cancer; ZW25; JZP598; HER-2 positive BIliary Tract cancer; Intrahepatic Cholangiocarcinoma (ICC); Extrahepatic Cholangiocarcinoma (ECC); Zanidatamab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Durvalumab; Pembrolizumab; Gemcitabine
• Other Study ID Numbers: JZP598-302; 2023-508219-21-00 (Other Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No