Clinical trial NCT05618327: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2022-11-16
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: MTD
timeFrame: Throughout the dose escalation and dose expansion phases,, an average of 1.5 years
measure: RP2D
timeFrame: Throughout the dose escalation and dose expansion phases, an average of 1.5 years
Secondary outcomes:
measure: DLT events
timeFrame: Up to 2 years
measure: Adverse events (AEs)
timeFrame: Up to 2 years
measure: Serious adverse events (SAEs)
timeFrame: Up to 2 years
measure: abnormal changes in clinically significant laboratory tests and other examinations
timeFrame: Up to 2 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
measure: Complete Response (CR)
timeFrame: Up to 2 years
measure: Duration of Objective Response (DOR)
timeFrame: Up to 2 years
measure: Duration of Complete Response (DOCR)
timeFrame: Up to 2 years
measure: Time to Response(TTR)
timeFrame: Up to 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Antidrug antibodies (ADA) and/or neutralizing antibodies (Nab)
timeFrame: At pre-defined intervals up to 2 years
measure: Total exposure(AUC) of JS203
timeFrame: At pre-defined intervals up to 2 years
measure: Maximum Plasma Concentration (Cmax) of JS203
timeFrame: At pre-defined intervals up to 2 years
measure: Half-life(T1/2) of JS203
timeFrame: At pre-defined intervals up to 2 years
measure: Clearance(CL) of JS203
timeFrame: At pre-defined intervals up to 2 years
measure: Volume of Distribution (Vss) of JS203
timeFrame: At pre-defined intervals up to 2 years
measure: Pharmacodynamic (PD) characteristics
timeFrame: At pre-defined interval up to 2 years
measure: Pharmacodynamic (PD) characteristics
timeFrame: At pre-defined interval up to 2 years
measure: Pharmacodynamic (PD) characteristics
timeFrame: At pre-defined interval up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Yuqin Song, MD
role: PRINCIPAL_INVESTIGATOR
References: