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

Phase 3

Recruiting

• Conditions: Biliary Tract Cancer
• Interventions: Drug: Zanidatamab; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pembrolizumab; Drug: Durvalumab

• Registration Number: NCT06282575
• Lead Sponsor: Jazz Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-02-21
• Study First Submitted QC: 2024-02-21
• Study First Posted: 2024-02-28
• Study Start: 2024-07-19
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-15
• Last Update Posted: 2025-09-17
• Primary Completion: 2028-12-01
• Study Completion: 2030-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 286

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zanidatamab with Standard-of-care Therapy Arm	Zanidatamab	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.
Zanidatamab with Standard-of-care Therapy Arm	Cisplatin	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.
Zanidatamab with Standard-of-care Therapy Arm	Gemcitabine	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.
Zanidatamab with Standard-of-care Therapy Arm	Pembrolizumab	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.
Zanidatamab with Standard-of-care Therapy Arm	Durvalumab	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.
Standard-of-care Therapy Arm	Cisplatin	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.
Standard-of-care Therapy Arm	Gemcitabine	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.
Standard-of-care Therapy Arm	Pembrolizumab	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.
Standard-of-care Therapy Arm	Durvalumab	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of participants achieving Confirmed objective response rate (cORR)	Up to 68 months	Confirmed objective response rate is defined as achieving a confirmed best overall response of Complete Response (CR) or Partial Response (PR)
Overall survival (OS) in participants with IHC 3+ tumors	Up to 68 months	OS is defined as the time from randomization to death, due to any cause.
Progression Free Survival for all participants	Up to 68 months	PFS is defined as the time from the date of randomization to the date of documented disease progression, or death from any cause.
Duration of response (DOR)	Up to 68 months	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.
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
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)	Up to 68 months	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.
TDD for all participants in patient-reported symptoms scores as measured by the EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain, and Pruritis)	Up to 68 months	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.
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	Up to 68 months	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
TDD for all participants in patient-reported PF domain score as measured by the EORTC QLQ-C30	Up to 68 months	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.
OS for all participants	Up to 68 months	OS is defined as the time from randomization to death, due to any cause.

Trial Locations

Locations (178)

The First Affiliated Hospital of USTC(Anhui Provincial Hospital); 🇨🇳 Hefei, Anhui, China

The First Hospital of Lanzhou University; 🇨🇳 Lanzhou, Gansu, China

Fondazione Policlinico Universitario Gemelli-IRCCS; 🇮🇹 Roma, Italy

Rocky Mountain Cancer Centers, LLP; 🇺🇸 Lone Tree, Colorado, United States

AdventHealth Hematology and Oncology; 🇺🇸 Orlando, Florida, United States

Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

The University of Kansas Cancer Center - Westwood; 🇺🇸 Westwood, Kansas, United States

Norton Cancer Institute - Audubon; 🇺🇸 Louisville, Kentucky, United States

Ochsner Clinic Foundation; 🇺🇸 New Orleans, Louisiana, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

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