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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: JS019

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yilong Wu, bachelor's degree; Phone Number: 86020-83877855; Email: syylwu@live.cn
• Study Contact Backup: Name: Huajun Chen, Doctor of Medicine; Phone Number: 8613710581145; Email: chenhuajun@gdph.org.cn

Study Locations

• China
  • Guangzhou
    • Guangdong, Guangzhou, China, 510062
      • Recruiting
      • Guangdong General Hospital
      • Contact: Yilong Wu, bachelor's degree; Phone Number: 86020-83877855; Email: syylwu@live.cn
      • Principal Investigator: Huajun Chen, Doctor of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be able to understand and willing to sign the Informed Consent Form;
2. Male or female aged 18~75 years (included);
3. Patients with pathologically confirmed advanced malignant solid tumors
4. Failed or unsuitable for standard treatment;
5. Eastern Cooperative Oncology Group (ECOG) physical fitness score: 0~1;
6. Expected survival period ≥ 12 weeks;
7. At least one measurable lesion according to criteria RECIST v1.1 ;

Exclusion Criteria:

1. Patients with known hypersensitivity to the components of JS019;
2. Patients who have received the treatment with anti-CD39 antibodies or inhibitors;
3. 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;
4. 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;
5. 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.);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: dose level：0.3mg/kg; Dose Escalation: 0.3mg/kg, IV infusion, every 3 weeks (q3w).	Biological: JS019; 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.
Experimental: Dose Escalation: dose level：1 mg/kg; Dose Escalation: 1 mg/kg IV infusion, every 3 weeks (q3w).	Biological: JS019; 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.
Experimental: Dose Escalation: dose level：3 mg/kg; Dose Escalation: 3 mg/kg IV infusion, every 3 weeks (q3w).	Biological: JS019; 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.
Experimental: Dose Escalation: dose level：10 mg/kg; Dose Escalation: 10 mg/kg IV infusion, every 3 weeks (q3w).	Biological: JS019; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Suzhou Kebo Ruijun Biotechnology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Anticipated): June 15, 2024
• Study Completion (Anticipated): August 10, 2024

Study Registration Dates

• First Submitted: August 10, 2022
• First Submitted That Met QC Criteria: August 17, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: JS019-002-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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