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

Phase 1

Recruiting

• Conditions: Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
• Interventions: Drug: JS203 for Injection

• Registration Number: NCT05618327
• Lead Sponsor: Shanghai Junshi Bioscience Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-10-20
• Study First Submitted QC: 2022-11-11
• Study First Posted: 2022-11-16
• Study Start: 2023-02-13
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-09
• Last Update Posted: 2024-07-11
• Primary Completion: 2024-12-24
• Study Completion: 2025-02-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 219

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
JS203	JS203 for Injection	-

Primary Outcome Measures

Name	Time	Method
RP2D	Throughout the dose escalation and dose expansion phases, an average of 1.5 years	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 .
MTD	Throughout the dose escalation and dose expansion phases,, an average of 1.5 years	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China