A Phase I, Open, Multicenter Clinical Study to Evaluate the Safety, Tolerance, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of JMKX000197 Injection in the Treatment of Malignant Pleural Effusion
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicity
研究概览
简要总结
A Phase I, Open, Multicenter Clinical Study to Evaluate the Safety, Tolerance, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of JMKX000197 Injection in the Treatment of Malignant Pleural Effusion
详细描述
Primary objectives: To evaluate the safety and tolerability of JMKX000197 injection in the treatment of patients with malignant pleural effusion, explore DLT of JMKX000197 treatment, and determine MTD and RP2D.
Secondary objectives: To evaluate the pharmacokinetic (PK)/pharmacokinetic (PD) characteristics of JMKX000197 injection in the treatment of patients with malignant pleural effusion; To evaluate preliminarily efficacy of JMKX000197 injection in patients with malignant pleural effusion; To evaluate the drug metabolic transformation of JMKX000197 injection.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient voluntarily joined the study, signed an informed consent form, and had good compliance.
- •Age ≥ 18 years and ≤ 75 years old, regardless of gender.
- •Malignant pleural effusion confirmed by histopathology or cytopathology as moderate or above and requiring drainage (definition of moderate pleural effusion: pleural effusion ≥ 3cm in lying position by B-ultrasound, pleural effusion ≥ 4cm in sitting position by B-ultrasound, accompanied by clinical symptoms such as chest tightness, shortness of breath, and discomfort).
- •Karnofsky score ≥ 60, or physical fitness score (ECOG PS) ≤
- •Expected survival time ≥ 3 months.
- •Within 7 days before treatment, the main organ function meets the following criteria: blood routine examination criteria (without blood transfusion within 14 days): neutrophil count ≥ 1.5 × 10 ^ 9 /L, Hemoglobin ≥ 9g/dL, Platelets ≥ 100 × 10 ^ 9 /L, White blood cells ≥ 3.0 × 10 ^ 9 /L; Biochemical examination indicators should meet: total bilirubin ≤ 1.5 × ULN, ALT≤2.5 × ULT, AST≤2.5 × ULT, if accompanied by liver metastasis, ALT and AST ≤ 5 × ULN, Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60ml/min; International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN.
- •No intrathoracic drug injection was performed within 1 month before signing the informed consent form, but diagnostic puncture is not excluded.
- •Women of reproductive age should agree to use contraception (such as intrauterine devices, birth control pills, or condoms) during the study period and within 6 months after the end of the study; The serum pregnancy test was negative within 7 days before enrollment and must be a non lactating patient; Men should agree to use effective contraception during the study period and within 6 months after the end of the study period.
排除标准
- •Known allergies to the study drug or its excipient components.
- •The location of pleural effusion is not suitable for drainage or the patient will not benefit from intrathoracic medication (e.g., severe separation).
- •Have used interferon gene stimulating factor (STING) agonists, TNF drugs (such as Tianenfu) for thoracic injection.
- •Have participated in other clinial trials within 4 weeks before signing the informed consent form.
- •Have a history of immunodeficiency, including a positive test for human immunodeficiency virus (HIV) antibodies, or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation.
- •Uncontrollable systemic infections (viruses, bacteria, fungi), including but not limited to hepatitis B surface antigen positive and hepatitis B virus DNA > 1000 IU/ml, hepatitis C virus (HCV) antibody positive or RNA positive.
- •According to the judgment of the researcher, the patient is not suitable for participating in this clinical study for any reason.
研究组 & 干预措施
JMKX000197 Dose 1
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
JMKX000197 Dose 2
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
JMKX000197 Dose 3
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
JMKX000197 Dose 4
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
JMKX000197 Dose 5
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
JMKX000197 Dose 6
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
JMKX000197 Dose 7
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
JMKX000197 Dose 8
eight dose levels of JMKX000197 are evaluated in the dose escalation part.In the expansion cohort part, the biologically active dose(s) confirmed in the dose escalation part with one or more dosing regimens will be selected.
干预措施: JMKX000197 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicity
时间窗: Up to approximately 7 days at each dose level
Recommended Phase II dose
时间窗: Up to approximately 24 months
Maximum tolerated dose
时间窗: Up to approximately 24 months
次要结局
- Objective Response Rate（ORR）(Up to approximately 36 days)
- Time to maximum concentration (Tmax) of JMKX000197(Up to approximately 7 days)
- Half-life (t1/2) of JMKX000197(Up to approximately 7 days)
- Concentrations of IL-6 in plasma(Up to approximately 36 days)
- Disease control rate, DCR(Up to approximately 36 days)
- Areas under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of JMKX000197(Up to approximately 7 days)
- Areas under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC0-t) of JMKX000197(Up to approximately 7 days)
- Amount of Drug Excreted Via Urine and excrement During the Collection Interval 0-48 Hours Post Administration(Up to approximately 48 hours)
- Maximum observed concentration (Cmax) of JMKX000197(Up to approximately 7 days)