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Phase I Clinical Study of JS203 in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Primary Purpose

Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
JS203 for Injection
Sponsored by
Shanghai Junshi Bioscience Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Understand and voluntarily sign the informed consent form. Age 18 - 75 years (both 18 and 75 years), both sexes Expected survival of ≥ 12 weeks. Eastern Collaborative Oncology Group (ECOG) physical status score: 0 to 1. B-cell non-Hodgkin's lymphoma expressing CD20 antigen clearly diagnosed by pathology Patients with non-Hodgkin's lymphoma must have measurable lesions that meet the Lugano 2014 criteria for lymphoma efficacy assessment, requiring lymph node lesions >1.5 cm in either length or extra-nodal lesions >1.0 cm in either length. Exclusion Criteria: history of severe allergy or anaphylactic reaction to monoclonal antibody therapy (or recombinant antibody-associated fusion protein). previous treatment with CD20-CD3 bispecific antibodies. failure to resolve toxicity after prior antitumor therapy, i.e., no return to baseline or grade 0-1 as defined by NCI-CTCAE 5.0 (except for alopecia, hyperpigmentation). Irreversible toxicity that is not reasonably expected to be exacerbated by the study drug and may be enrolled upon confirmation with the sponsor. Received antitumor therapy such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, or biologic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose. Non-tumor related conditions that are amenable to hormone therapy (e.g. insulin therapy for diabetes and hormone replacement therapy). receive autologous hematopoietic stem cell transplantation within 100 days prior to the first dose have undergone, or are expected to require during the study period, major surgery (as judged by the investigator) or are recovering from surgery within 4 weeks prior to the first dose active hepatitis B or C. Active hepatitis B defined as positive for hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) with HBV DNA above the upper limit of the study center's normal value; active hepatitis C defined as positive for hepatitis C antibody and HCV RNA above the upper limit of the study center's normal value. history of cardiac disease: New York Heart Association (NYHA) > Class II congestive heart failure, myocardial infarction occurring within 6 months prior to enrollment, or arrhythmia requiring antiarrhythmic therapy and/or left ventricular ejection fraction < 50%. two or more malignancies within 5 years prior to the first dose. Except for early malignancies that have been eradicated (carcinoma in situ or stage I tumors), such as adequately treated cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer. persons with uncontrollable psychiatric disorders patients with a history of drug abuse or alcohol abuse other conditions judged by the investigator to be inappropriate for participation in this study, including but not limited to having any disease or medical history that may confound study results and interfere with patient compliance

Sites / Locations

  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

JS203

Arm Description

Outcomes

Primary Outcome Measures

MTD
It is suitable for dose escalation and dose extension.If the number of DLT patients is 0 and the next higher dose is unacceptable, the current dose is declared MTD.
RP2D
It is suitable for dose escalation and dose extension.RP2D will be determined based on a combination of safety, tolerability, PK and/or pharmacodynamic studies .

Secondary Outcome Measures

DLT events
Incidence and severity of DLT events.
Adverse events (AEs)
Incidence and severity of adverse events (AEs)
Serious adverse events (SAEs)
Incidence and severity of serious adverse events (SAEs).
abnormal changes in clinically significant laboratory tests and other examinations
abnormal changes in clinically significant laboratory tests and other examinations
Objective Response Rate (ORR)
Objective Response Rate (ORR) as Assessed by Investigator according to Lugano 2014
Complete Response (CR)
Complete Response (CR) as Assessed by Investigator according to Lugano 2014
Duration of Objective Response (DOR)
Duration of Objective Response (DOR) as Assessed by Investigator
Duration of Complete Response (DOCR)
Duration of Complete Response (DOCR) as Assessed by Investigator
Time to Response(TTR)
Time to Response(TTR) as Assessed by Investigator
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) as Determined by Investigator
Overall Survival (OS)
Overall Survival (OS)
Antidrug antibodies (ADA) and/or neutralizing antibodies (Nab)
incidence of antidrug antibodies (ADA) and/or neutralizing antibodies (Nab)
Total exposure(AUC) of JS203
Total exposure(AUC) of JS203
Maximum Plasma Concentration (Cmax) of JS203
Maximum Plasma Concentration (Cmax) of JS203
Half-life(T1/2) of JS203
Half-life(T1/2) of JS203
Clearance(CL) of JS203
Clearance(CL) of JS203
Volume of Distribution (Vss) of JS203
Volume of Distribution (Vss) of JS203
Pharmacodynamic (PD) characteristics
CD20 receptor occupancy rate in peripheral blood cells
Pharmacodynamic (PD) characteristics
Changes in peripheral blood immune cell subtypes (B cells, T cells) before and after drug administration.
Pharmacodynamic (PD) characteristics
Changes in peripheral blood cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) before and after drug administration

Full Information

First Posted
October 20, 2022
Last Updated
July 27, 2023
Sponsor
Shanghai Junshi Bioscience Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05618327
Brief Title
Phase I Clinical Study of JS203 in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Official Title
Phase I Clinical Study of JS203 in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 13, 2023 (Actual)
Primary Completion Date
December 24, 2024 (Anticipated)
Study Completion Date
February 22, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Junshi Bioscience Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is an open phase I clinical study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, pharmacodynamic (PD) profile, immunogenicity, and preliminary efficacy of JS203 in patients with relapsed/refractory B-cell non-Hodgkin's lymphoma. The study is divided into three phases: a dose-escalation phase, a dose-expansion phase, and an efficacy expansion phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
219 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
JS203
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
JS203 for Injection
Intervention Description
2-steps:JS203 for Injection is administered on the first and eighth day of the first cycle and every 3 weeks thereafter. 3-steps:JS203 for Injection is administered on the first, eighth and fifteenth day of the first cycle and every 3 weeks thereafter. 4-steps:JS203 for Injection is administered on the first, eighth, fifteenth and twenty-second day of the first cycle and every 3 weeks thereafter.
Primary Outcome Measure Information:
Title
MTD
Description
It is suitable for dose escalation and dose extension.If the number of DLT patients is 0 and the next higher dose is unacceptable, the current dose is declared MTD.
Time Frame
Throughout the dose escalation and dose expansion phases,, an average of 1.5 years
Title
RP2D
Description
It is suitable for dose escalation and dose extension.RP2D will be determined based on a combination of safety, tolerability, PK and/or pharmacodynamic studies .
Time Frame
Throughout the dose escalation and dose expansion phases, an average of 1.5 years
Secondary Outcome Measure Information:
Title
DLT events
Description
Incidence and severity of DLT events.
Time Frame
Up to 2 years
Title
Adverse events (AEs)
Description
Incidence and severity of adverse events (AEs)
Time Frame
Up to 2 years
Title
Serious adverse events (SAEs)
Description
Incidence and severity of serious adverse events (SAEs).
Time Frame
Up to 2 years
Title
abnormal changes in clinically significant laboratory tests and other examinations
Description
abnormal changes in clinically significant laboratory tests and other examinations
Time Frame
Up to 2 years
Title
Objective Response Rate (ORR)
Description
Objective Response Rate (ORR) as Assessed by Investigator according to Lugano 2014
Time Frame
Up to 2 years
Title
Complete Response (CR)
Description
Complete Response (CR) as Assessed by Investigator according to Lugano 2014
Time Frame
Up to 2 years
Title
Duration of Objective Response (DOR)
Description
Duration of Objective Response (DOR) as Assessed by Investigator
Time Frame
Up to 2 years
Title
Duration of Complete Response (DOCR)
Description
Duration of Complete Response (DOCR) as Assessed by Investigator
Time Frame
Up to 2 years
Title
Time to Response(TTR)
Description
Time to Response(TTR) as Assessed by Investigator
Time Frame
Up to 2 years
Title
Progression-Free Survival (PFS)
Description
Progression-Free Survival (PFS) as Determined by Investigator
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Description
Overall Survival (OS)
Time Frame
Up to 2 years
Title
Antidrug antibodies (ADA) and/or neutralizing antibodies (Nab)
Description
incidence of antidrug antibodies (ADA) and/or neutralizing antibodies (Nab)
Time Frame
At pre-defined intervals up to 2 years
Title
Total exposure(AUC) of JS203
Description
Total exposure(AUC) of JS203
Time Frame
At pre-defined intervals up to 2 years
Title
Maximum Plasma Concentration (Cmax) of JS203
Description
Maximum Plasma Concentration (Cmax) of JS203
Time Frame
At pre-defined intervals up to 2 years
Title
Half-life(T1/2) of JS203
Description
Half-life(T1/2) of JS203
Time Frame
At pre-defined intervals up to 2 years
Title
Clearance(CL) of JS203
Description
Clearance(CL) of JS203
Time Frame
At pre-defined intervals up to 2 years
Title
Volume of Distribution (Vss) of JS203
Description
Volume of Distribution (Vss) of JS203
Time Frame
At pre-defined intervals up to 2 years
Title
Pharmacodynamic (PD) characteristics
Description
CD20 receptor occupancy rate in peripheral blood cells
Time Frame
At pre-defined interval up to 2 years
Title
Pharmacodynamic (PD) characteristics
Description
Changes in peripheral blood immune cell subtypes (B cells, T cells) before and after drug administration.
Time Frame
At pre-defined interval up to 2 years
Title
Pharmacodynamic (PD) characteristics
Description
Changes in peripheral blood cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) before and after drug administration
Time Frame
At pre-defined interval up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Understand and voluntarily sign the informed consent form. Age 18 - 75 years (both 18 and 75 years), both sexes Expected survival of ≥ 12 weeks. Eastern Collaborative Oncology Group (ECOG) physical status score: 0 to 1. B-cell non-Hodgkin's lymphoma expressing CD20 antigen clearly diagnosed by pathology Patients with non-Hodgkin's lymphoma must have measurable lesions that meet the Lugano 2014 criteria for lymphoma efficacy assessment, requiring lymph node lesions >1.5 cm in either length or extra-nodal lesions >1.0 cm in either length. Exclusion Criteria: history of severe allergy or anaphylactic reaction to monoclonal antibody therapy (or recombinant antibody-associated fusion protein). previous treatment with CD20-CD3 bispecific antibodies. failure to resolve toxicity after prior antitumor therapy, i.e., no return to baseline or grade 0-1 as defined by NCI-CTCAE 5.0 (except for alopecia, hyperpigmentation). Irreversible toxicity that is not reasonably expected to be exacerbated by the study drug and may be enrolled upon confirmation with the sponsor. Received antitumor therapy such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, or biologic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose. Non-tumor related conditions that are amenable to hormone therapy (e.g. insulin therapy for diabetes and hormone replacement therapy). receive autologous hematopoietic stem cell transplantation within 100 days prior to the first dose have undergone, or are expected to require during the study period, major surgery (as judged by the investigator) or are recovering from surgery within 4 weeks prior to the first dose active hepatitis B or C. Active hepatitis B defined as positive for hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) with HBV DNA above the upper limit of the study center's normal value; active hepatitis C defined as positive for hepatitis C antibody and HCV RNA above the upper limit of the study center's normal value. history of cardiac disease: New York Heart Association (NYHA) > Class II congestive heart failure, myocardial infarction occurring within 6 months prior to enrollment, or arrhythmia requiring antiarrhythmic therapy and/or left ventricular ejection fraction < 50%. two or more malignancies within 5 years prior to the first dose. Except for early malignancies that have been eradicated (carcinoma in situ or stage I tumors), such as adequately treated cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer. persons with uncontrollable psychiatric disorders patients with a history of drug abuse or alcohol abuse other conditions judged by the investigator to be inappropriate for participation in this study, including but not limited to having any disease or medical history that may confound study results and interfere with patient compliance
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhihao Jiang
Phone
86-15350403639
Email
zhihao_jiang@junshipharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuqin Song, MD
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wanli Shen
Phone
86-010-88196393
Email
gcp_shenwl@bjcancer.org

12. IPD Sharing Statement

Learn more about this trial

Phase I Clinical Study of JS203 in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

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