An Open-label, Multi-center, Phase I/II Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of MRG002 in Combination With HX008 in Patients With HER2-expressed Advanced Malignant Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Incidence of dose limiting toxicity (DLT) in each dose group
研究概览
简要总结
The objective of this study is to assess the safety and tolerability of MRG002 in combination with HX008 in patients with HER2-expressed advanced malignant solid tumors; and to , explore the maximum tolerated dose (MTD), and to determine the recommended phase II dose (RP2D) of combination therapy; , and to evaluate the preliminary efficacy, pharmacokinetics, and immunogenicity of combination therapy in the targeted study population.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing to sign the informed consent form and follow the requirements specified in the protocol.
- •Aged 18 to 75 (including 18 and 75), both genders.
- •Life expectancy ≥ 12 weeks.
- •Patients with histopathological or cytological confirmed HER2-expressed advanced solid tumors, and with at least one measurable lesion according to the Response Criteria in Solid Tumors (RECIST v1.1).
- •The score of ECOG for performance status is 0 or
- •The toxicity of previous anti-tumor treatment has recovered to ≤ Grade 1 as defined by NCI-CTCAEv5.
- •No severe cardiac dysfunction.
- •Organ functions must meet the basic requirements.
- •Cumulative dose of anthracycline ≤ 450 mg/m2 doxorubicin or its equivalent.
排除标准
- •Prior treatment with chemotherapy, biological therapy, immunotherapy, radiotherapy, investigational drugs, attenuated live vaccines, immunomodulators, CYP3A4 inhibitors/inducers, antibody-drug conjugates, etc.
- •Treatment with immune checkpoint inhibitors or tumor vaccines within 60 days prior to the first dose.
- •Treatment with systemic corticosteroids or other immunosuppressive drugs within 14 days prior to the first dose or during the study period.
- •History of severe cardiac disease.
- •Poorly controlled hypertension and hyperglycemia.
- •Presence of peripheral neuropathy ≥ Grade
- •History of moderate or severe dyspnea at rest due to advanced malignant tumor or its complications or severe primary pulmonary disease, or current need of continuous oxygen therapy, or current interstitial lung disease or pneumonia.
- •Central nervous system metastasis.
- •Received major surgery within 4 weeks prior to the first dose without complete recovery.
- •History of hypersensitivity to any component of MRG002 or HX008 or known history of hypersensitivity of ≥ Grade 3 to macromolecular protein products/monoclonal antibodies.
- •Evidence of active infection.
- •History of primary immunodeficiency or autoimmune disease.
- •Female patients with a positive serum pregnancy test or who are breast-feeding or who do not agree to take adequate contraceptive measures during the treatment and for 6 months after the last dose of study treatment.
- •Previous history of other primary malignancies.
- •Other conditions inappropriate for participation in this study, as deemed by the investigator.
研究组 & 干预措施
MRG002+HX008
MRG002 will be administrated via intravenous infusion at 1.8，,2.2, or 2.6 mg/kg , (if appropriate) once on Day 1 of every 3 weeks (21-day cycle), up to 24 months.
HX008 will be administrated via intravenous infusion at 3 mg/kg once on Day 1 of every 3 weeks (21-day- cycle), up to 24 months.
干预措施: MRG002+HX008 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicity (DLT) in each dose group
时间窗: Within 28 days after the first dose.
DLT is defined as any of the treatment emergent adverse events (TEAE) as specified in the protocol that bear a definite, probable, or possible causal relationship to study drug administration within 28 days after the first dose.
Adverse events
时间窗: After signing informed consent until 90 days after the last dose.
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.
Recommended Phase II Dose (RP2D)
时间窗: Baseline to study completion (up to 24 months)
The dose level of MRG002 recommended for further clinical studies based on assessment of the safety, efficacy and PK data from this study.
次要结局
- Progression Free Survival (PFS)(Baseline to study completion (up to 24 months))
- Overall Survival (OS)(Baseline to study completion (up to 24 months))
- Time to Response (TTR)(Baseline to study completion (up to 24 months))
- Objective Response Rate (ORR)(Baseline to study completion (up to 24 months))
- Duration of Response (DOR)(Baseline to study completion (up to 24 months))
- PK parameters: concentration-time curve(Baseline to 90 days after the last dose.)
- Immunogenicity (ADA)(Baseline to 90 days after the last dose.)
- Disease Control Rate (DCR)(Baseline to study completion (up to 24 months))