A First-In-Human, Phase 1, Open-Label, Multicenter Study of ZW251, a Novel Glypican-3 Targeting Antibody-Drug Conjugate, in Participants With Advanced Solid Tumors, Including Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 26
- 主要终点
- Incidence of dose-limiting toxicities (DLTs; Part 1)
研究概览
简要总结
The purpose of this study is to find out if ZW251, an antibody-drug conjugate targeting glypican-3 (GPC3), is safe and can treat participants with advanced cancers, including hepatocellular carcinoma (HCC), squamous cell non-small cell lung cancer (NSCLC), or germ cell tumors (GCT).
详细描述
Part 1 (dose escalation) of the study will evaluate the safety and tolerability of ZW251 in HCC, squamous cell NSCLC, and GCT. Part 2 (dose optimization) of the study will further assess safety and potential anti-tumor activity of the ZW251 established recommended doses in HCC.
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
- •Pathologically or cytologically confirmed diagnosis of HCC with evidence of locally advanced (unresectable, and ineligible for transplant) and/or metastatic disease. Noninvasive methods may be used to confirm diagnosis
- •Pathologically or cytologically confirmed diagnosis of squamous cell NSCLC with evidence of locally advanced (unresectable) and/or metastatic disease
- •Pathologically or cytologically confirmed diagnosis of GCT with evidence of yolk sac and/or choriocarcinoma predominant component and locally advanced (unresectable) and/or metastatic disease
- •Measurable disease per RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •Liver function status of Child-Pugh Class A (for HCC only)
- •Adequate organ function
排除标准
- •Known additional malignancy that is progressing or that has required active treatment within the last year
- •History of hepatic encephalopathy within the past 6 months or requirement for medications to control encephalopathy
- •Participants with HCC experiencing main portal vein tumor invasion require sponsor approval for enrollment
- •Known gastrointestinal bleeding within 3 months
- •Acute or chronic uncontrolled renal disease, pancreatitis, or non-malignant liver disease
研究组 & 干预措施
ZW251
干预措施: ZW251 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs; Part 1)
时间窗: Up to 3 weeks
Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW251
Incidence of AEs (Parts 1 and 2)
时间窗: Up to approximately 2 years
Number of participants who experienced AEs, adverse events of special interest, or serious adverse events
Incidence of clinical laboratory abnormalities (Parts 1 and 2)
时间窗: Up to approximately 2 years
Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0
Confirmed objective response rate (Part 2)
时间窗: Up to approximately 2 years
Number of participants who achieved a best overall response of either confirmed complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Objective response rate (Part 2)
时间窗: Up to approximately 2 years
Number of participants who achieved a best overall response of either confirmed complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
次要结局
- Area under the concentration-time curve of ZW251 at steady state (AUCtau,ss; Parts 1 and 2)(Up to approximately 2 years)
- Confirmed objective response rate (Part 1)(Up to approximately 2 years)
- Best overall response (Parts 1 and 2)(Up to approximately 2 years)
- Disease control rate (Parts 1 and 2)(Up to approximately 2 years)
- Duration of response (Parts 1 and 2)(Up to approximately 2 years)
- Progression-free survival (Parts 1 and 2)(Up to approximately 2 years)
- Overall survival (Part 2)(Up to approximately 2 years)
- Area under the concentration-time curve (AUC0-504) of ZW251 (Parts 1 and 2)(Up to approximately 2 years)
- Maximum concentration (Cmax) of ZW251 (Parts 1 and 2)(Up to approximately 2 years)
- Maximum concentration of ZW251 at steady state (Сmax,ss; Parts 1 and 2)(Up to approximately 2 years)
- Minimal concentration of ZW251 at steady state (Сmin,ss; Parts 1 and 2)(Up to approximately 2 years)
- Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)(Up to approximately 2 years)
- Objective response rate (Part 1)(Up to approximately 2 years)
- Progression-free survival (Part 2)(Up to approximately 2 years)