Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Conditions
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.
Interventions
DRUGJS203 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.
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious adverse events (SAEs) | Up to 2 years | Incidence and severity of serious adverse events (SAEs). |
| abnormal changes in clinically significant laboratory tests and other examinations | Up to 2 years | abnormal changes in clinically significant laboratory tests and other examinations |
| Objective Response Rate (ORR) | Up to 2 years | Objective Response Rate (ORR) as Assessed by Investigator according to Lugano 2014 |
| Complete Response (CR) | Up to 2 years | Complete Response (CR) 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 |
| Duration of Complete Response (DOCR) | Up to 2 years | Duration of Complete Response (DOCR) as Assessed by Investigator |
| Time to Response(TTR) | Up to 2 years | Time to Response(TTR) as Assessed by Investigator |
| Progression-Free Survival (PFS) | Up to 2 years | Progression-Free Survival (PFS) as Determined by Investigator |
| DLT events | Up to 2 years | Incidence and severity of DLT events. |
| 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) |
| Total exposure(AUC) of JS203 | At pre-defined intervals up to 2 years | Total exposure(AUC) of JS203 |
| Maximum Plasma Concentration (Cmax) of JS203 | At pre-defined intervals up to 2 years | Maximum Plasma Concentration (Cmax) of JS203 |
| Half-life(T1/2) of JS203 | At pre-defined intervals up to 2 years | Half-life(T1/2) of JS203 |
| 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 |
| Pharmacodynamic (PD) characteristics | At pre-defined interval up to 2 years | CD20 receptor occupancy rate in peripheral blood cells |
| Overall Survival (OS) | Up to 2 years | Overall Survival (OS) |
| Adverse events (AEs) | Up to 2 years | Incidence and severity of adverse events (AEs) |
Countries
China
Outcome results
None listed