A Clinical Study to Evaluate the Safety, Tolerability,JS019 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of JS019 as monotherapy in patients with advanced malignant solid tumors The study includes JS019 monotherapy dose escalation, dose expansion stages to investigate the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of JS019 as monotherapy.

Detailed Description
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Monotherapy Dose Escalation Stage: In this stage, the safety and tolerability, PK characteristics, immunogenicity and pharmacodynamics characteristics of JS019 are investigated. Four dosage groups are preset: 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg. The drug is administered intravenously every 3 weeks (Q3W). A treatment cycle is 21 days, with a DLT observation period of 21 days after the initial administration. The incremental dose and dosing interval may be adjusted as necessary during the study based on safety, PK, and other results obtained Monotherapy Dose Expansion Stage: According to RP2D of JS019 single drug dose, 3-5 specific tumor types are selected for indication expansion, and about 8-12 patients are enrolled for each indication. Tumor types and additional cases could be selected according to the specific situation in the trial process. It is planned to expand the cohort of lung cancer, pancreatic cancer, sarcoma, hepatocellular carcinoma, cholangiocarcinoma and other solid tumors to explore the efficacy and safety of JS019 single drug. The specific cohort will be adjusted according to the results of previous studies.

Official Title
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A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Recombinant Fully Human Anti-CD39 Monoclonal Antibody JS019 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: JS019


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able to understand and willing to sign the Informed Consent Form; Male or female aged 18 75 years (included); Patients with pathologically confirmed advanced malignant solid tumors Failed or unsuitable for standard treatment; Eastern Cooperative Oncology Group (ECOG) physical fitness score: 0 1; Expected survival period ≥ 12 weeks; At least one measurable lesion according to criteria RECIST v1.1 ; Exclusion Criteria: Patients with known hypersensitivity to the components of JS019; Patients who have received the treatment with anti-CD39 antibodies or inhibitors; Patients who participated in other clinical studies within 4 weeks prior to the first administration of JS019, except patients are in the follow-up period of observational (non-interventional) clinical study or interventional study; Patients who have received major surgery within 4 weeks before the first dose or expected to undergo major surgery during the study (as judged by the investigator) or are in the recovery period from surgery; Patients who have received anti-tumor therapy, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, or biological therapy, within 4 weeks or 5 half-lives of the therapy (whichever is shorter) prior to the first dose of JS019. Patients who have received traditional Chinese medicine or Chinese patent medicine preparations with anti-tumor indications within 2 weeks before the first dose of JS019. Can accept hormone therapy for non-tumor-related diseases (such as insulin therapy for diabetes and hormone replacement therapy, etc.);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: dose level：0.3mg/kg<br>Dose Escalation: 0.3mg/kg, IV infusion, every 3 weeks (q3w). | Biological: JS019<br>* Four dose levels are preset: 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg. The subjects are treated with JS019 by intravenous infusion, once every 3 weeks (Q3W). A treatment cycle is 21 days, and the DLT observation period is 21 days after the first administration.<br>|
| Experimental: Dose Escalation: dose level：1 mg/kg<br>Dose Escalation: 1 mg/kg IV infusion, every 3 weeks (q3w). | Biological: JS019<br>* Four dose levels are preset: 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg. The subjects are treated with JS019 by intravenous infusion, once every 3 weeks (Q3W). A treatment cycle is 21 days, and the DLT observation period is 21 days after the first administration.<br>|
| Experimental: Dose Escalation: dose level：3 mg/kg<br>Dose Escalation: 3 mg/kg IV infusion, every 3 weeks (q3w). | Biological: JS019<br>* Four dose levels are preset: 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg. The subjects are treated with JS019 by intravenous infusion, once every 3 weeks (Q3W). A treatment cycle is 21 days, and the DLT observation period is 21 days after the first administration.<br>|
| Experimental: Dose Escalation: dose level：10 mg/kg<br>Dose Escalation: 10 mg/kg IV infusion, every 3 weeks (q3w). | Biological: JS019<br>* Four dose levels are preset: 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg. The subjects are treated with JS019 by intravenous infusion, once every 3 weeks (Q3W). A treatment cycle is 21 days, and the DLT observation period is 21 days after the first administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Incidence of DLT severity of adverse events (AEs) and serious adverse events (SAEs)and tolerability | Incidence of DLT, incidence and severity of adverse events (AE) and severe adverse events (SAE), clinically significant abnormal laboratory changes and other tests | 2 years | 
| Maximum Tolerated Dose (MTD) or Optimal Biological Effect Dose (OBD) and Phase II study recommended dose (RP2D) | The safety, pharmacokinetic and preliminary efficacy data of the comprehensive dose escalation were determined. When MTD/OBD is determined, MTD/OBD is usually used as RP2D. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) | Drug concentrations in individual subjects at different time points after administration | 2 years | 
| Immunogenicity | Incidence of anti-drug antibodies (ADA), titer of ADA-positive samples. | 2 years | 
| Pharmacodynamics （PD） | CD39 receptor occupancy in peripheral blood. | 2 years | 
| Objective response rate (ORR) | The percentage of cases with remission (PR + CR) after treatment was assessable | 2 years | 
| Duration of response (DOR) | The time from the first assessment of CR or PR to the first assessment of PD or death due to any cause. | 2 years | 
| Disease control rate (DCR) | The percentage of cases with remission (PR + CR) and stable lesions (SD) after treatment was assessable. | 2 years | 
| Time to response (TTR) | time from the start of treatment to progression of diease. | 2 years | 
| Progression-free survival (PFS) | PFS is defined as time from the start of treatment to progression of disease or death. | 2 years | 
| Overall survival (OS) | Overall survival is defined as time from the start of treatment until death due to any reason. | 2 years |