A Phase I Study of JMKX000197 Injection in the Treatment of Malignant Pleural Effusion

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

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 Overview

• Status: Recruiting
• Conditions: Malignant Pleural Effusion
• Intervention / Treatment: Drug: JMKX000197

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: jianping Su; Phone Number: +86 15162481262; Email: sujianping@jemincare.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430062
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Jianying Huang; Phone Number: +86 18971116998; Email: znyylcsy@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: JMKX000197; for injection
Experimental: 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.	Drug: JMKX000197; for injection
Experimental: 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.	Drug: JMKX000197; for injection
Experimental: 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.	Drug: JMKX000197; for injection
Experimental: 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.	Drug: JMKX000197; for injection
Experimental: 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.	Drug: JMKX000197; for injection
Experimental: 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.	Drug: JMKX000197; for injection
Experimental: 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.	Drug: JMKX000197; for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose limiting toxicity	Up to approximately 7 days at each dose level
Maximum tolerated dose	Up to approximately 24 months
Recommended Phase II dose	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate（ORR）	Up to approximately 36 days
Disease control rate, DCR	Up to approximately 36 days
Maximum observed concentration (Cmax) of JMKX000197	Up to approximately 7 days
Time to maximum concentration (Tmax) of JMKX000197	Up to approximately 7 days
Half-life (t1/2) of JMKX000197	Up to approximately 7 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
Concentrations of IL-6 in plasma	Up to approximately 36 days

Collaborators and Investigators

• Sponsor: Jemincare
• Collaborators: Zhejiang Hangyu Pharmaceutical Co., Ltd
• Investigators: Principal Investigator: Jianying Huang, Zhongnan Hospital of Wuhan University，No. 169, Donghu Road, Wuchang District, Wuhan, Hubei

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: June 25, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 25, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion
• Other Study ID Numbers: JY-JM-0197-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No