Safety, Tolerability, Pharmacokinetics & Pharmacodynamics of an Anti-PD-1 mAb for Patients With Advanced Solid Tumors

NCT02836834 | Unknown Phase 1 DMC

• 1 other identifier: Junshi-JS001-YKZL-I
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to assess the safety and tolerability of JS-001 in subjects with various advanced or recurrent malignancies, including solid tumors and lymphomas, 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. The exploratory objectives include to evaluate the consistency between biomarker detection results of archived tissue and fresh frozen tissue, and to assess the consistency of response using various response criteria (such as irRC, WHO, RECIST and irRECIST).

Conditions

Lymphoma; Lung Cancer

Keywords

immunotherapy; check point inhibitor; PD-1 antibody; solid tumor; lymphoma; phase 1 trial

Outcome Measures

Primary Outcomes (1)

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

  154 days

Secondary Outcomes (1)

• correlation analysis of PD-L1 expression of tumor and ORR

  154 days

Study Arms (3)

Dose Escalation Cohort

EXPERIMENTAL

JS001

Biological: JS001

Expanded cohort 1

EXPERIMENTAL

The subjects of expanded cohort 1 will use repeated doses every 2 weeks like multiple dose cohorts

Biological: JS001

Expanded cohort 2

EXPERIMENTAL

The subjects of expanded cohort 2 will use repeated doses every 2 weeks like multiple dose cohorts

Biological: JS001

Interventions

JS001 BIOLOGICAL

Dose escalation study evaluating three dose levels (1, 3 and 10 mg/kg) of JS-001.Each of the 3 dose levels will use 2 dose schedules: single dose, and repeated doses every 2 weeks. Subjects will be assigned to a dose schedule in the order of study entry.

Also known as: toripalimab, TAB001

Dose Escalation Cohort; Expanded cohort 1; Expanded cohort 2

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;
• No standard of care for the patient;
• At least 1 measurable lesion;
• Aged 18-65 years;
• Anticipated life expectancy of at least 3 months;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• i) At least 4 weeks elapsed since receiving systemic chemotherapy, at least 6 weeks since receiving mitomycin or nitrosoureas, and at least 2 weeks since receiving a tyrosine kinase inhibitor;
• At least 4 weeks elapsed since receiving definite radiotherapy, and at least 2 weeks since receiving palliative 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;

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;
• 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)

Cancer Hospital Chinese Academy of Medical Science

Beijing, Beijing Municipality, 100021, China

Location

Related Publications (1)

• Yang J, Dong L, Yang S, Han X, Han Y, Jiang S, Yao J, Zhang Z, Zhang S, Liu P, Qin Y, Wu H, Feng H, Yao S, Sun Y, Song H, Shi Y. Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study. Eur J Cancer. 2020 May;130:182-192. doi: 10.1016/j.ejca.2020.01.028. Epub 2020 Mar 27.

  PMID: 32224416 DERIVED

MeSH Terms

Conditions

Lymphoma; Lung Neoplasms

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yuankai Shi, PhD.MD

  Cancer Hospital Chinese Academy of Medical Science

  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: July 13, 2016
• First Posted: July 19, 2016
• Study Start: August 1, 2016
• Primary Completion: September 1, 2020
• Study Completion: December 1, 2020
• Last Updated: October 22, 2019

Record last verified: 2019-10

Locations

CN (1)