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

Malignant Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03316144
• Other study ID #: Junshi-JS001-011
• Status: Completed
• Phase: Phase 1
• Start date: July 12, 2017
• Est. completion date: December 30, 2019

Study information

• Verified date: September 2020
• Source: Shanghai Junshi Bioscience Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: December 30, 2019
• Est. primary completion date: September 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Malignant Lymphoma

Intervention

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.

Locations

Country	Name	City	State
China	Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Junshi Bioscience Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0		6 months
Secondary	correlation analysis of PD-L1 expression of tumor		6 months
Secondary	Objective Response Rate (ORR) by irRC and RECIST 1.1		6 months