Safety and Efficacy of Toripalimab for Patients With Locally Advanced or Metastatic Bladder Urothelial Carcinoma

NCT03113266 | Unknown Phase 2 DMC

• 1 other identifier: Junshi-JS001-009
• Study Type: interventional
• Target: 370
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open-label, phase 2 study evaluating the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with locally advanced or metastatic bladder urothelial carcinoma who have failed in routine systemic treatment.

Conditions

Bladder Urothelial Carcinoma

Keywords

anti-PD-1 monoclonal antibody; Metastatic; Advanced; Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by RECIST 1.1 and irRECIST

  The treatment effect of JS001 will be assessed using irRC and RECIST 1.1 to determine tumor response.

  3 years

Secondary Outcomes (5)

• Duration of response (DOR) by RECIST1.1 and irRECIST

  3 years

• Progression free survival (PFS) by RECIST1.1 and irRECIST

  3 years

• Overall survival (OS)

  3 years

• Immunogenicity of anti-PD-1 monoclonal antibody

  3 years

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

  3 years

Other Outcomes (2)

• Correlation analysis of PD-L1 expression of tumor by ORR

  3 years

• Correlation analysis of PD-L1 expression of tumor by Immunohistochemistry

  3 years

Study Arms (1)

humanized anti-PD-1monoclonal antibody

EXPERIMENTAL

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

Biological: humanized anti-PD-1 monoclonal antibody toripalimab

Interventions

humanized anti-PD-1 monoclonal antibody toripalimab BIOLOGICAL

humanized anti-PD-1 monoclonal antibody (JS001) is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.

Also known as: JS001, TAB001

humanized anti-PD-1monoclonal antibody

Eligibility Criteria

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

You may qualify if:

• Male and Female aged 18 and older are eligible;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• Histologic diagnosis of locally advanced or metastatic bladder urothelial carcinoma, including the origin of renal pelvis, ureter, urinary tract;
• At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan \>=20mm, spiral CT scan \>=10mm, no prior radiation to measurable lesions);
• Providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes);
• Predicted survival \>=3 months;
• Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 3 months (prior systemic steroids was allowed, but concurrent administration of systemic steroids with the study drug is excluded).
• Screening laboratory values must meet the following criteria（within past 14 days）:
• hemoglobin ≥ 9.0 g/dL; neutrophils ≥ 1500 cells/ µL; platelets ≥ 100 x 10\^3/ µL; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1╳ULN，creatinine clearance \>50ml/min (Cockcroft-Gault equation) INR, aPTT≤1.5 x ULN; Urine protein + 1 or less, if the urine protein \> 1 +, need to collect 24 hours urinary protein determination, the total amount should be 1 gram or less
• Without systemic steroids within past 4 weeks
• Males or female of childbearing potential must: agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 12 months after the last dose of study drug.
• Must have read, understood, and provided written informed consent voluntarily. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

You may not qualify if:

• Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody, including auxiliary treatment phase
• Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Abm or its components
• Prior antitumor therapy (including corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment;
• Pregnant or nursing;
• Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (\>500IU/ml);
• HBsAg or HBcAb with positive test for HBV DNA (\>500IU/ml)
• History with active tuberculosis;
• Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;
• Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure \> class II NYHA, heart block \>II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm);
• Evidence with active CNS disease;
• Prior live vaccine therapy within past 4 weeks;
• Received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• Prior major surgery within past 4 weeks (diagnostic surgery excluded);
• Psychiatric medicines abuse without withdrawal, or history of psychiatric illness;
• Associated with clinical symptoms or symptomatic treatment of pleural effusion or ascites;

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jun Guo

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ling Xiao

CONTACT

051286876925; ling_xiao@topalliancebio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 13, 2017
• Study Start: April 6, 2017
• Primary Completion: March 15, 2020
• Study Completion: February 1, 2022
• Last Updated: September 30, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)