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

NCT03316144 | Completed Phase 1 DMC

• 1 other identifier: Junshi-JS001-011
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Lymphoma

Keywords

immunotherapy; check point inhibitor; PD-1 antibody; phase 1 trial; Malignant Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  6 months

Secondary Outcomes (2)

• correlation analysis of PD-L1 expression of tumor

  6 months

• Objective Response Rate (ORR) by irRC and RECIST 1.1

  6 months

Study Arms (3)

1 mg/kg Toripalimab

EXPERIMENTAL

humanized anti-PD-1 monoclonal antibody is to be injected intravenously 1mg/kg Q2w until disease progresses or unacceptable tolerability occurs

Biological: Toripalimab

3 mg/kg Toripalimab

EXPERIMENTAL

humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w until disease progresses or unacceptable tolerability occurs

Biological: Toripalimab

10 mg/kg Toripalimab

EXPERIMENTAL

humanized anti-PD-1 monoclonal antibody is to be injected intravenously 10mg/kg Q2w until disease progresses or unacceptable tolerability occurs

Biological: Toripalimab

Interventions

Toripalimab BIOLOGICAL

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.

Also known as: JS001, TAB001

1 mg/kg Toripalimab; 10 mg/kg Toripalimab; 3 mg/kg Toripalimab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (1)

Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Lymphoma

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Junyuan Qi, MD, PhD

  Blood Diseases Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: October 20, 2017
• Study Start: July 12, 2017
• Primary Completion: September 15, 2018
• Study Completion: December 30, 2019
• Last Updated: September 30, 2020

Record last verified: 2020-09

Locations

CN (1)