Clinical trial NCT05923515: A Phase I Study of JMKX000197 Injection in the Treatment of Malignant Pleural Effusion
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Malignant Pleural Effusion
Lead sponsor: Jemincare
Sponsor class: INDUSTRY
Collaborators: name: Zhejiang Hangyu Pharmaceutical Co., Ltd.
First posted: 2023-06-28
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. The patient voluntarily joined the study, signed an informed consent form, and had good compliance.
2. Age ≥ 18 years and ≤ 75 years old, regardless of gender.
3. 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).
4. Karnofsky score ≥ 60, or physical fitness score (ECOG PS) ≤ 2.
5. Expected survival time ≥ 3 months.
6. 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.
7. No intrathoracic drug injection was performed within 1 month before signing the informed consent form, but diagnostic puncture is not excluded.
8. 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.

Exclusion Criteria:

1. Known allergies to the study drug or its excipient components.
2. The location of pleural effusion is not suitable for drainage or the patient will not benefit from intrathoracic medication (e.g., severe separation).
3. Have used interferon gene stimulating factor (STING) agonists, TNF drugs (such as Tianenfu) for thoracic injection.
4. Have participated in other clinial trials within 4 weeks before signing the informed consent form.
5. 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.
6. 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.
7. According to the judgment of the researcher, the patient is not suitable for participating in this clinical study for any reason.

Primary outcomes:
measure: Incidence of dose limiting toxicity
timeFrame: Up to approximately 7 days at each dose level
measure: Maximum tolerated dose
timeFrame: Up to approximately 24 months
measure: Recommended Phase II dose
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Objective Response Rate（ORR）
timeFrame: Up to approximately 36 days
measure: Disease control rate, DCR
timeFrame: Up to approximately 36 days
measure: Maximum observed concentration (Cmax) of JMKX000197
timeFrame: Up to approximately 7 days
measure: Time to maximum concentration (Tmax) of JMKX000197
timeFrame: Up to approximately 7 days
measure: Half-life (t1/2) of JMKX000197
timeFrame: Up to approximately 7 days
measure: Areas under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of JMKX000197
timeFrame: Up to approximately 7 days
measure: Areas under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC0-t) of JMKX000197
timeFrame: Up to approximately 7 days
measure: Amount of Drug Excreted Via Urine and excrement During the Collection Interval 0-48 Hours Post Administration
timeFrame: Up to approximately 48 hours
measure: Concentrations of IL-6 in plasma
timeFrame: Up to approximately 36 days
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
affiliation: Zhongnan Hospital of Wuhan University，No. 169, Donghu Road, Wuchang District, Wuhan, Hubei
name: Jianying Huang
role: PRINCIPAL_INVESTIGATOR
References: