Biliary Tract Cancer
Conditions
Keywords
JZP598, ZW25, HER-2 positive BIliary Tract cancer, Gallbladder Cancer, Intrahepatic Cholangiocarcinoma (ICC), Extrahepatic Cholangiocarcinoma (ECC), Zanidatamab, HER-2 overexpression, HER-2 amplification
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.
Interventions
DRUGZanidatamab
Administered intravenously (IV)
DRUGCisplatin
Administered intravenously (IV)
DRUGGemcitabine
Administered intravenously (IV)
DRUGPembrolizumab
Administered intravenously (IV)
DRUGDurvalumab
Administered intravenously (IV)
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| OS for all participants | Up to 68 months | OS is defined as the time from randomization to death, due to any cause. |
| 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) |
| 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 | — |
| 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. |
| 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. |
Countries
Argentina, Belgium, Brazil, Canada, Chile, China, Czechia, Finland, France, Germany, India, Israel, Italy, Japan, Portugal, Puerto Rico, Romania, Serbia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTClinical Trial Disclosure & Transparency
Outcome results
None listed