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

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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Lymphoma
• Intervention / Treatment: Biological: Toripalimab

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Blood Diseases Hospital, Chinese Academy of medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1 mg/kg Toripalimab; humanized anti-PD-1 monoclonal antibody is to be injected intravenously 1mg/kg Q2w until disease progresses or unacceptable tolerability occurs	Biological: Toripalimab; 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.; Other Names: JS001, TAB001
EXPERIMENTAL: 3 mg/kg Toripalimab; humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w until disease progresses or unacceptable tolerability occurs	Biological: Toripalimab; 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.; Other Names: JS001, TAB001
EXPERIMENTAL: 10 mg/kg Toripalimab; humanized anti-PD-1 monoclonal antibody is to be injected intravenously 10mg/kg Q2w until disease progresses or unacceptable tolerability occurs	Biological: Toripalimab; 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.; Other Names: JS001, TAB001

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: Junyuan Qi, MD, PhD, Blood Diseases Hospital, Chinese Academy of medical Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 12, 2017
• Primary Completion (ACTUAL): September 15, 2018
• Study Completion (ACTUAL): December 30, 2019

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: October 18, 2017
• First Posted (ACTUAL): October 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: immunotherapy; Malignant Lymphoma; PD-1 antibody; phase 1 trial; check point inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: Junshi-JS001-011

Drug and device information, study documents

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