NCT05311397进行中（未招募）1 期
A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of A166 in Patients With Unresectable, Locally Advanced or Metastatic HER2-expressing Solid Tumors (KL166-I-01-CTP)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a single arm, open-label, dose-escalation and dose-expansion phase I study evaluating A166 in patients with HER2-expressing locally advanced or metastatic solid tumors.
详细描述
The first stage will determine the recommended stage 2 dose (RS2D) in patients with unresectable, locally advanced or metastatic HER2-expressing solid tumors based on safety, tolerability, pharmacokinetic characteristics and antitumor activity. The second stage will assess the safety, tolerability, pharmacokinetic characteristics and antitumor activity in dose-expansion cohorts (RS2D:3.6 mg/kg, 4.8 mg/kg and 6.0 mg/kg dose groups).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Voluntarily sign informed consent form;
- •Age ≥ 18 years old, no gender limit;
- •Patients had a histologically confirmed incurable locally advanced or metastatic solid tumors;
- •Determined HER2-positive disease (detected by ISH or NGS) or HER2-expressing disease by evaluation or detection. Definition of HER2 expression in this study: Immunohistochemistry [IHC] ≥ 1＋;
- •Patients unable to benefit from the available standard treatment according to the judgment of the investigator;
- •White blood cell count (WBC) ≥ 4.0×109/L or ≥ lower limit of normal value; Neutrophil count (NEUT) ≥ 1.5×109/L; Platelet count (PLT) ≥ 100×109/L; Hemoglobin concentration ≥ 9.0 g/dL;
- •Total bilirubin (TBIL) ≤ 1.5×ULN. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN). For patients with liver metastases, ALT and AST ≤ 5 times ULN, and for patients with liver and/or bone metastases, alkaline phosphatase ≤ 5 times ULN;
- •Creatinine clearance rate ≥ 50 ml/min;
- •Patients had an Eastern Cooperative Oncology Group (ECOG)performance status of 0 or 1, the expected survival time is ≥ 3 months;
- •During the study period and within 7 months after the final administration of A166, patients with fertility (regardless of male and female) must receive effective medical contraceptive measures;
- •The patients must recover from all acute toxicities of the previous treatment (relieved to grade 1 or baseline), except for hair loss and vitiligo;
排除标准
- •Severe or uncontrollable heart disease requiring treatment, or grade 3 or 4 congestive heart failure according to the New York Society of Cardiology (NYHA), or unstable angina pectoris that cannot be controlled by drugs, or history of myocardial infarction within 6 months prior to enrollment, or severe arrhythmia requiring medical treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia);
- •History of ≥ Grade 3 allergic reaction to trastuzumab;
- •Permanent with drawal of trastuzumab due to any previous toxicity;
- •Patients with brain metastases who have symptoms or who have received the radiotherapy or surgery within 3 months before the first administration;
- •Patients requiring oxygen therapy in daily activities;
- •Grade 2 or higher peripheral neuropathy;
- •Any chemotherapy, hormone therapy (except dexamethasone), radiotherapy, immunotherapy or biological therapy received within 4 weeks before the first administration;
- •Prior-treatment with other clinical research drugs within 4 weeks before the first administration;
- •Patients who have undergone major surgery within 4 weeks before the first administration;
- •Active hepatitis B (hepatitis B surface antigen positive and HBV-DNA higher than the upper limit of reference value) or hepatitis C (positive hepatitis C virus antibody and HCV-RNA higher than the upper limit of reference value); current or past alcoholics ; Liver cirrhosis;
- •Known active human immunodeficiency virus (HIV);
- •Systemic diseases that cannot be controlled, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, glaucoma, etc according to investigator's judgment;
- •Current pregnancy or lactation;
- •QTc interval> 470 ms according to the baseline measurement:;
- •Left ventricular ejection fraction (LVEF) <45% according to the echocardiogram (ECHO) or multi-gate circuit controlled acquisition (MUGA) ;
- •Previous cumulative doxorubicin accumulation > 360 mg/m2 or its equivalent dose;
研究组 & 干预措施
The first stage（Dose-escalation）
Experimental
According to the initial dose, the highest dose and the modified Fibonacci method, the dose escalation of A166 for injection is designed as: 0.1 mg/kg, 0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg, 4.8 mg/kg (the highest dose is tentatively set at 4.8 mg/kg).
干预措施: A166 (Drug)
The second stage（Dose-expansion）
Experimental
The administered dose of A166 for injection is RS2D obtained in the first stage .
干预措施: A166 (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: up to 24 month
The percentage of patients with CR and PR assessed by investigators according to RECIST v 1.1
次要结局
- Overall Survival (OS)(up to 24 month)
- Duration of Response (DOR)(up to 24 month)
- Progression-free survival(PFS)(up to 24 month)
研究者
研究点 (1)
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