NCT04466891已完成2 期
A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 67
- 主要终点
- Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)
研究概览
简要总结
This multicenter, open-label, single-arm trial will evaluate the anti-tumor activity of ZW25 (zanidatamab) monotherapy in subjects with human epidermal growth factor receptor 2 (HER2)-amplified, inoperable and advanced or metastatic biliary tract cancer (BTC), including intra-hepatic cholangiocarcinoma (ICC), extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 BTC, including ICC, ECC or GBC.
- •Locally advanced or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
- •Received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who received gemcitabine in prior adjuvant or neoadjuvant treatment, if progression occurred < 6 months from the latter of primary surgical resection or completion of gemcitabine-containing adjuvant therapy, they will be considered as having received 1 prior line of therapy for advanced disease.
- •Subjects must test positive for HER2 amplification by ISH-assay at a central laboratory on a new biopsy or archival tissue. Note that fine needle aspirates (FNAs; cytology samples) and biopsies from sites of bone metastases are not acceptable. Testing may occur at any time after diagnosis of advanced or metastatic disease and before study enrollment.
- •Male or female, ≥18 years of age (or the legal age of adulthood per country-specific regulations).
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate organ function.
- •Adequate cardiac function, as defined by left ventricular ejection fraction ≥ 50%.
排除标准
- •Received systemic anti-cancer therapy within 3 weeks of the first dose of ZW
- •Received radiotherapy within 2 weeks of the first dose of ZW
- •Prior treatment with HER2-targeted agents.
- •Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks at the time of screening).
- •Known leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the investigator, the subject must be free of neurological symptoms of LMD.
- •Concurrent uncontrolled or active hepatobiliary disorders or untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, unresolved biliary obstruction, infected biloma or abscess. Any complications must be resolved more than 2 weeks prior to the first dose of ZW
- •Prior or concurrent malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- •Active hepatitis
- •Infection with human immunodeficiency virus (HIV)-1 or HIV-2
- •QTc Fridericia (QTcF) > 470 ms.
- •History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease.
- •Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease.
研究组 & 干预措施
ZW25 (Zanidatamab) Monotherapy
Experimental
干预措施: ZW25 (Zanidatamab) (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)
时间窗: Up to 34 months
Number of participants who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is defined as a disappearance of all target and non-target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of all target lesions.
次要结局
- Duration of Response (DOR) by ICR(Up to 45 months)
- DOR ≥ 16 Weeks by ICR(24 weeks, up to 45 months)
- Disease Control Rate (DCR) by ICR(Up to 45 months)
- Progression-free Survival (PFS) by ICR(Up to 45 months)
- ORR by Investigator Assessment(Up to 45 months)
- DOR by Investigator Assessment(Up to 45 months)
- DOR ≥ 16 Weeks by Investigator Assessment(24 weeks, up to 45 months)
- DCR by Investigator Assessment(Up to 45 months)
- PFS by Investigator Assessment(Up to 45 months)
- Overall Survival(Up to 45 months)
- Incidence of Adverse Events (AEs)(Up to 45 months)
- Incidence of Laboratory Abnormalities(Up to 45 months)
- Maximum Serum Concentration of ZW25(Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose)
- Trough Concentration of ZW25(Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose)
- Incidence of Anti-drug Antibodies (ADAs)(Up to 45 months)
研究者
研究点 (67)
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相关资讯
FDA Grants Accelerated Approval to Zanidatamab for HER2-Positive Biliary Tract Cancer• The FDA granted accelerated approval to zanidatamab for pretreated, unresectable or metastatic HER2-positive biliary tract cancer on November 20, 2024.
• The approval was based on the phase 2b HERIZON-BTC-01 trial, which showed a 52% overall response rate in patients treated with zanidatamab.
• Zanidatamab is a HER2-directed bispecific antibody, marking the first accelerated approval of a HER2-targeted agent for this difficult-to-treat cancer.
• A confirmatory phase 3 trial, HERIZON-BTC-302, is underway to investigate zanidatamab plus standard-of-care therapy in the frontline setting.last yearZanidatamab Approved for HER2+ Biliary Tract Cancer• The FDA granted accelerated approval to zanidatamab for previously treated, unresectable or metastatic HER2-positive biliary tract cancer.
• Zanidatamab, a dual HER2-targeted bispecific antibody, achieved a 52% overall response rate in the HERIZON-BTC-01 trial.
• The estimated duration of response to zanidatamab was 14.9 months, offering a chemotherapy-free option for this patient population.last yearFDA Grants Accelerated Approval to Zanidatamab for HER2-Positive Biliary Tract Cancer• The FDA has granted accelerated approval to zanidatamab-hrii (Ziihera) for previously treated, unresectable or metastatic HER2-positive biliary tract cancer.
• Approval was based on the HERIZON-BTC-01 trial, which demonstrated a 52% objective response rate and a median duration of response of 14.9 months.
• Zanidatamab, a bispecific HER2-directed antibody, is administered intravenously every two weeks at a dose of 20 mg/kg until disease progression or unacceptable toxicity.
• The FDA also approved the Ventana PATHWAY anti-HER-2/neu antibody as a companion diagnostic to identify patients eligible for zanidatamab treatment.last yearFDA Grants Accelerated Approval to Zanidatamab for HER2+ Biliary Tract Cancer• The FDA has granted accelerated approval to zanidatamab-hrii (Ziihera) for treating adults with previously treated unresectable or metastatic HER2+ biliary tract cancer (BTC).
• The approval was based on positive objective response rate (ORR) and duration of response (DOR) data from the HERIZON-BTC-01 clinical trial.
• Zanidatamab is a dual HER2-targeted bispecific antibody, offering a chemotherapy-free treatment option for patients with HER2+ BTC.
• Continued approval is contingent upon verification of clinical benefits in the confirmatory Phase 3 HERIZON-BTC-302 trial.last yearFDA Grants Accelerated Approval to Jazz Pharmaceuticals' Ziihera for HER2-Positive Biliary Tract Cancer• The FDA granted accelerated approval to Jazz Pharmaceuticals’ Ziihera (zanidatamab-hrii) for HER2-positive biliary tract cancer (BTC) after prior treatment.
• Ziihera, a bispecific antibody, offers a chemotherapy-free option for BTC patients, potentially improving their quality of life and overall survival rates.
• The approval was based on Phase IIb HERIZON-BTC-01 trial data, demonstrating a 41.3% objective response rate in evaluable patients.
• Median overall survival in the trial's cohort 1 was 15.5 months, with 18.1 months in patients with HER2-positive IHC 3+ disease.last year
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