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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: JS203 for Injection

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Understand and voluntarily sign the informed consent form.
2. Age 18 - 75 years (both 18 and 75 years), both sexes
3. Expected survival of ≥ 12 weeks.
4. Eastern Collaborative Oncology Group (ECOG) physical status score: 0 to 1.
5. B-cell non-Hodgkin's lymphoma expressing CD20 antigen clearly diagnosed by pathology
6. 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:

1. history of severe allergy or anaphylactic reaction to monoclonal antibody therapy (or recombinant antibody-associated fusion protein).
2. previous treatment with CD20-CD3 bispecific antibodies.
3. 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.
4. 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).
5. receive autologous hematopoietic stem cell transplantation within 100 days prior to the first dose
6. 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
7. 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.
8. 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%.
9. 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.
10. persons with uncontrollable psychiatric disorders
11. patients with a history of drug abuse or alcohol abuse
12. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JS203

Drug: JS203 for Injection; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Throughout the dose escalation and dose expansion phases,, an average of 1.5 years
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 .	Throughout the dose escalation and dose expansion phases, an average of 1.5 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: Yuqin Song, MD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: November 11, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: JS203-001-I

Drug and device information, study documents

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