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

Phase 3RecruitingNCT06282575

Jazz Pharmaceuticals286 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

286

Conditions

Biliary Tract Cancer

Interventions

ZanidatamabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 which is limited to Cisplatin and Gemcitabine (CisGem) 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. 13. Use of phenytoin

Locations (183)

City of Hope(City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, United States

RECRUITING

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, United States

ACTIVE_NOT_RECRUITING

AdventHealth Hematology and Oncology

Orlando, Florida, United States

RECRUITING

Winship Cancer Institute

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to 52 months

Secondary Outcomes

Overall survival (OS) in participants with IHC 3+ tumors

OS is defined as the time from randomization to death, due to any cause.

Time frame: 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.

Time frame: Up to 68 months

OS for all participants

OS is defined as the time from randomization to death, due to any cause.

Time frame: 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)

Time frame: 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.

Time frame: Up to 68 months

Number of Patients reporting Treatment-Emergent Adverse Events (TEAE)

Time frame: Up to 68 months

Maximum serum concentration of Zanidatamab

Time frame: Up to 68 months

Number of participants who develop Anti-drug antibodies (ADAs) to Zanidatamab

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 68 months

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

Overview

Conditions

Interventions

Eligibility

Locations (183)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts