An Open-Label, Multi-center, Phase I/II Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Anti-Tumor Activity and Pharmacokinetics of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 14
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The objective of this study is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of MRG004A in patients with Tissue Factor positive advanced or metastatic solid tumors.
详细描述
This study consists of two parts. Part A is a dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of MRG004A. Part B is a disease specific multi-cohort dose expansion study to further assess the efficacy and safety of MRG004A at confirmed RP2D.
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
- •Understands and provides written informed consent and willing to follow the requirements specified in protocol.
- •Age ≥18 years.
- •Life expectancy ≥6 months.
- •For Part B patients, documented Tissue Factor (TF) presence in tumor biopsy specimens obtained from archival or re-biopsy specimens by immunohistochemistry (IHC) protein expression.
- •Must have histologically or cytologically confirmed unresectable or metastatic cancer with documented disease progression during prior therapy, or relapse or progression following approved standard therapy for their tumor types- Part A and Part B.
- •Part B: Patients who have documented progression during or relapse following standard therapy, no further treatment options that are known to improve survival, and participation in a clinical trial is a reasonable therapeutic option.
- •Patients must have measurable disease per RECIST v1.
- •ECOG performance status of 0 or
- •Acceptable bone marrow, hepatic, cardiac, renal, and coagulation function.
- •A negative serum pregnancy test if female and aged between 18-55 years old.
- •Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for 180 days after the last infusion of MRG004A.
排除标准
- •Archival or biopsy tumor shows TF IHC membrane or cytosolic score of zero, no TF-positive expression or no TF-positive staining in Part B patients.
- •Toxicities (except alopecia & fatigue) due to prior antitumor therapy are greater than CTCAE v5.0 Grade
- •Toxicities due to prior radiotherapy that have not resolved to Grade ≤ 1 CTCAE v5.0 at least 21 days prior to the first treatment.
- •Untreated, unstable or uncontrolled central nervous system (CNS) metastases.
- •Any other type of anti-cancer therapy within 21 days of the first dose of study treatment. Use of any other type of anti-cancer treatment is prohibited throughout the study.
- •Patients with increased bleeding risk.
- •Presence of severe cardiac dysfunction.
- •Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug.
- •Concurrent malignancy within 5 years prior to entry.
- •Uncontrolled or poorly controlled hypertension.
- •History of ventricular tachycardia, or torsade des pointes.
- •History of moderate to severe dyspnea at rest.
- •Major surgery within 4 weeks of the first dose of study treatment and not fully recovered. Minor surgery within 2 weeks prior to study treatment.
- •Known allergic reactions to any component or excipient of MRG004A or known allergic reactions to other prior anti-TF (including investigational) or other monoclonal antibody ≥ Grade
- •Patients who have any known liver disease, including chronic hepatitis B, hepatitis C, autoimmune hepatic disorders, primary biliary cirrhosis or sclerosing cholangitis; Patients who have concurrent, serious, uncontrolled infections or known infection with HIV, or have a diagnosed acquired immunodeficiency syndrome (AIDS); or an uncontrolled autoimmune disease, or have undergone organ transplant.
- •Active uncontrolled bacterial, viral, fungal, rickettsial, or parasitic infection.
- •Use of systemic corticosteroids within 4 weeks prior to the first dose of treatment.
- •Use of strong CYP3A4 inhibitors or inducers with MRG004A.
- •Other excluded medications or treatment: therapeutic anti-coagulative, or long-term anti-platelet treatment; multivitamins, calcium, vitamin D, and prophylactic anti-RANKL (denosumab) and zoledronic acid therapies for bone metastases are allowed.
- •Any patient with a positive pregnancy or is breast-feeding.
- •Any severe and/or uncontrolled systemic disease that at the discretion of investigator and sponsor makes it undesirable for the patient to participate in this study.
研究组 & 干预措施
MRG004A
All patients in Part A (dose escalation) and Part B (dose expansion) will be administrated MRG004A on Day 1 of every 3 weeks (21-day cycle).
干预措施: MRG004A (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Baseline to study completion (up to 24 months)
The proportion of patients who achieve complete response (CR) or partial response (PR) as assessed by the Independent Central Review (ICR).
Maximum Tolerated Dose (MTD)
时间窗: DLT will be evaluated during the first treatment cycle (Day 1-21)
The highest dose confirmed wherein less than 2 out of 6, or \< 33% of evaluable patients in a treatment cohort experiences dose-limiting toxicity (DLT).
Recommended Phase II Dose (RP2D)
时间窗: Baseline to study completion (up to 24 months)
The dose level of MRG004A recommended for further clinical studies based on assessment of the safety, efficacy and PK data from Part A of this study.
Adverse Events (AEs)
时间窗: From signing informed consent until 45 days after the last dose of MRG004A
Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.
次要结局
- Disease Control Rate (DCR)(Baseline to study completion (up to 24 months))
- Pharmacokinetics (PK) Parameter of MRG004A: Tmax(Baseline to 30 days after the last dose of study treatment)
- Incidence of anti-drug antibody (ADA)(Baseline to 30 days after the last dose of study treatment)
- Progression Free Survival (PFS)(Baseline to study completion (up to 24 months))
- Duration of Response (DoR)(Baseline to study completion (up to 24 months))
- Pharmacokinetics (PK) Parameter of MRG004A: Cmax(Baseline to 30 days after the last dose of study treatment)
- Overall Survive (OS)(Baseline to study completion (up to 24 months))
- Pharmacokinetics (PK) Parameter of MRG004A: AUClast(Baseline to 30 days after the last dose of study treatment)