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

Biliary Tract Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06282575
• Other study ID #: JZP598-302
• Secondary ID: 2023-508219-21-0
• Status: Recruiting
• Phase: Phase 3
• Start date: April 30, 2024
• Est. completion date: November 1, 2029

Study information

• Verified date: April 2024
• Source: Jazz Pharmaceuticals
• Contact: Clinical Trial Disclosure & Transparency
• Phone: 215-832-3750
• Email: ClinicalTrialDisclosure[@]JazzPharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 286
• Est. completion date: November 1, 2029
• Est. primary completion date: July 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms
• HER2 Gene Mutation

Intervention

Drug:
• Zanidatamab
Administered intravenously (IV)
• Cisplatin
Administered intravenously (IV)
• Gemcitabine
Administered intravenously (IV)
• Pembrolizumab
Administered intravenously (IV)
• Durvalumab
Administered intravenously (IV)

Locations

Country	Name	City	State
Puerto Rico	Hospital Oncologico, Puerto Rico Medical Center	Rio Piedras
United States	Texas Oncology - DFW	Dallas	Texas
United States	Rocky Mountain Cancer Centers, LLP	Lone Tree	Colorado
United States	Norton Cancer Institute - Audubon	Louisville	Kentucky
United States	Minnesota Oncology Hematology, P.A.	Maple Grove	Minnesota
United States	SCRI Oncology Partners	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	OS for all participants	OS is defined as the time from randomization to death, due to any cause.	Up to 68 months
Secondary	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
Secondary	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
Secondary	Number of Patients reporting Treatment-Emergent Adverse Events (TEAE)		Up to 68 months
Secondary	Maximum serum concentration of Zanidatamab		Up to 68 months
Secondary	Number of participants who develop Anti-drug antibodies (ADAs) to Zanidatamab		Up to 68 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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