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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 286
- 试验地点
- 427
- 主要终点
- Progression Free Survival (PFS) in participants with Immunohistochemistry (IHC) 3+ tumors
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
- •Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
- •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.
- •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.
- •Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
- •Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function
- •Females of childbearing potential must have a negative pregnancy test result.
- •Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.
排除标准
- •Prior treatment with a HER2-targeted agent
- •Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
- •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.
- •Use of systemic corticosteroids.
- •Brain metastases
- •Severe chronic or active infections
- •History of allogeneic organ transplantation.
- •Active or prior autoimmune inflammatory conditions
- •History of interstitial lung disease or non-infectious pneumonitis.
- •Participation in another clinical trial with an investigational medicinal product within the last 3 months.
- •Females who are breastfeeding
- •Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
- •Use of phenytoin
研究组 & 干预措施
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.
干预措施: Zanidatamab (Drug)
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.
干预措施: Cisplatin (Drug)
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.
干预措施: Gemcitabine (Drug)
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.
干预措施: Cisplatin (Drug)
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.
干预措施: Pembrolizumab (Drug)
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.
干预措施: Durvalumab (Drug)
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.
干预措施: Gemcitabine (Drug)
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.
干预措施: Durvalumab (Drug)
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.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS) in participants with Immunohistochemistry (IHC) 3+ tumors
时间窗: 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.
次要结局
- Number of participants achieving Confirmed objective response rate (cORR)(Up to 68 months)
- Overall survival (OS) in participants with IHC 3+ tumors(Up to 68 months)
- OS for all participants(Up to 68 months)
- Progression Free Survival for all participants(Up to 68 months)
- Duration of response (DOR)(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)
- 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 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)
- 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 for all participants in patient-reported PF domain score as measured by the EORTC QLQ-C30(Up to 68 months)
研究者
研究点 (427)
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