Safety, Tolerability, Pharmacokinetics & Pharmacodynamics of Toripalimab for Patients With Recurrent Malignant Lymphoma

Study Overview
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Brief Summary
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The primary objective is to assess the safety and tolerability of JS-001 in subjects with recurrent malignant lymphoma, and to evaluate its preliminary efficacy. The secondary objectives are to: 1) characterize the single-dose and multi-dose pharmacokinetic (PK) profile of JS-001, 2) characterize the immunogenicity of JS-001; 3) assess the dose-efficacy relationship of JS-001 single agent, and 4) preliminarily evaluate biomarkers associated with the efficacy of JS-001.

Official Title
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A Phase I Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Injection in Patients With Recurrent Malignant Lymphoma

Conditions
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Malignant Lymphoma

Intervention / Treatment
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* Biological: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to sign Informed Consent; Re-entry into the study is allowed with a second informed consent; Willing to provide blood sample for biomarker analysis(mandatory). The tissue sample is optional; A diagnosis of an advanced malignant tumor confirmed by histology or cytology (including typical Hodgkin's lymphoma and B cell source non-hodgkin's lymphoma); No standard of care for the patient; At least 1 measurable lesion; Aged 18-65 years; Anticipated life expectancy of at least 6 months; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; At least 4 weeks elapsed since receiving systemic chemotherapy; At least 4 weeks elapsed since receiving definite radiotherapy; At least 2 weeks since the last dose of systemic steroid therapy (>10 mg/day prednisone or equivalent); At least 4 weeks since receiving anti-cancer biotherapy; Recovered from previous treatment related adverse reaction; willing to use an acceptable contraceptive method; A negative pregnancy test for female subjects of childbearing potential; Exclusion Criteria: Active central nervous system (CNS) metastases and/or carcinomatous meningitis; Known history of another primary solid tumor, unless the participant has undergone potentially curative therapy with no evidence of that disease for 2 years, or underwent successful definitive resection of basal or squamous cell carcinoma of the skin, or in situ cervical cancer; Active, known or suspected autoimmune disease.Autoimmune diseases caused by lymphoma are not included in this list; Patients who have had car-T cell therapy Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibodies; Significant medical disease; Active infection; Active tuberculosis or history of tuberculosis with one year; Infection of Human immunodeficiency virus (HIV); A complication requiring immune-suppression; Received a live vaccine within 4 weeks prior to first dose of study drug pleural or abdominal effusion with symptoms; Drug or alcohol abuse (for subjects in the pharmacokinetic cohorts) ; evidence of interstitial lung disease; Active hepatitis B or C, or with significant risk of hepatitis reactivation; Known immediate or delayed hypersensitivity reaction or idiosyncrasy to monoclonal antibodies or drugs chemically related to the study drug. History of serious hypersensitivity reaction or serious hepatotoxicity related to any drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 mg/kg Toripalimab<br>humanized anti-PD-1 monoclonal antibody is to be injected intravenously 1mg/kg Q2w until disease progresses or unacceptable tolerability occurs | Biological: Toripalimab<br>* Dose escalation study evaluating three dose levels (1, 3 and 10 mg/kg) of JS001. Subjects will be assigned to a dose schedule in the order of study entry.<br>* Other names: JS001, TAB001;|
| Experimental: 3 mg/kg Toripalimab<br>humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w until disease progresses or unacceptable tolerability occurs | Biological: Toripalimab<br>* Dose escalation study evaluating three dose levels (1, 3 and 10 mg/kg) of JS001. Subjects will be assigned to a dose schedule in the order of study entry.<br>* Other names: JS001, TAB001;|
| Experimental: 10 mg/kg Toripalimab<br>humanized anti-PD-1 monoclonal antibody is to be injected intravenously 10mg/kg Q2w until disease progresses or unacceptable tolerability occurs | Biological: Toripalimab<br>* Dose escalation study evaluating three dose levels (1, 3 and 10 mg/kg) of JS001. Subjects will be assigned to a dose schedule in the order of study entry.<br>* Other names: JS001, TAB001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| correlation analysis of PD-L1 expression of tumor |  | 6 months | 
| Objective Response Rate (ORR) by irRC and RECIST 1.1 |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, check point inhibitor, PD-1 antibody, phase 1 trial, Malignant Lymphoma