An Open-Label, Dose-Finding, Phase I Study in Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 2
- 主要终点
- Dose Limiting Toxicity (DLT) - Phase Ia
研究概览
简要总结
The objective of this study is to assess the safety, efficacy, and pharmacokinetics of MRG003, as well as immunogenicity as defined by the incidence of anti-drug antibody (ADA) of MRG003 in patients with advanced solid tumors, including colorectal cancer, squamous cell carcinoma of head and neck, and nasopharyngeal carcinoma.
详细描述
This study consists of two parts: Phase Ia dose escalation and Phase Ib dose expansion. The objective of Phase Ia is to determine MTD or RP2D, and Phase Ib is conducted to evaluate efficacy of MRG003 in patients with advanced colorectal cancer, squamous cell carcinoma of head and neck (SCCHN), and nasopharyngeal carcinoma.
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
- •Willing to sign the ICF and follow the requirements specified in the protocol.
- •Age: ≥18 years and ≤75 years, both genders
- •Expected survival time≥12 weeks
- •Phase Ia: Patients with histologically and cytologically confirmed advanced or metastatic solid tumor
- •Phase Ib: Patients with histologically and cytologically confirmed EGFR-positive advanced or metastatic colorectal cancer, squamous cell carcinoma of head and neck, and nasopharyngeal carcinoma
- •Subjects must have measurable lesions according to the response Evaluation Criteria In Solid Tumors（RECIST v1.1）
- •ECOG performance score 0 or 1
- •Acceptable liver, renal, and hematologic function
- •Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment
排除标准
- •History of hypersensitivity to any component of the investigational product
- •Presence of central nervous system metastasis
- •Prior history of other primary malignancies
- •Known history of clinically significant hepatic diseases
- •Evidence of active infection of human immunodeficiency virus (HIV)
- •History of ophthalmic abnormalities
- •Any severe or uncontrolled systemic disease judged by the investigator
- •Patients with poorly controlled heart diseases
- •Received radiotherapy, chemotherapy, biotherapy, immunotherapy or other anti-tumor drugs within 4 weeks prior to the first dose of study treatment
- •Major surgery or surgical therapy for any cause within 4 weeks prior to the first dose of investigational drug
- •Planned surgery or surgery is the best interest of patients as determined by investigator
- •History of severe skin disease requiring interruption of previous EGFR targeted therapy; or chronic skin disease requiring oral or intravenous therapy
- •Active concomitant diseases that might increase risks of toxicity
- •Pregnancy, or breast feeding
研究组 & 干预措施
MRG003
Phase Ia: MRG003 will be administrated by an IV infusion of escalating doses (0.1, 0.3, 0.6, 1.0, 2.0, 2.5, 3.0 mg/kg) on Day 1 of every 3 weeks (Q3W); Phase Ib: MRG003 will be administrated by an IV infusion of MTD/RP2D.
干预措施: MRG003 (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT) - Phase Ia
时间窗: First cycle (21 days)
DLT is assessed on Day 21 (Day 1 to 21) of the first dose administration.
Objective Response Rate (ORR) - Phase Ib
时间窗: Baseline to study completion (up to 24 weeks)
ORR was defined as the proportions of subjects with a complete response (CR) and partial response (PR). ORR will be assessed by investigator according to RECIST v1.1.
次要结局
- PK parameter for MRG003: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)(Baseline to study completion (up to 24 weeks))
- PK parameter for MRG003: Maximum Drug Concentration (Cmax)(Baseline to study completion (up to 24 weeks))
- Immunogenicity(Baseline to study completion (up to 24 weeks))
- Progression Free Survival (PFS) - Phase Ib only(Baseline to study completion (up to 24 weeks))
- Duration of Response (DoR) - Phase Ib only(Baseline to study completion (up to 24 weeks))
- Overall Survival (OS) - Phase Ib only(Baseline to study completion (up to 24 weeks))
- Incidence of Adverse Events (AEs)(Baseline to 30 days after the last dose of study treatment)
- PK parameter for total antibody (TAb): Cmax(Baseline to study completion (up to 24 weeks))
- PK parameter for MMAE: AUClast(Baseline to study completion (up to 24 weeks))
- PK parameter for TAb: AUClast(Baseline to study completion (up to 24 weeks))
- PK parameter for Monomethyl Auristatin E (MMAE): Cmax(Baseline to study completion (up to 24 weeks))