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

A Phase II, Open, Multi-center and Single Arm Study Investigating Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Injection in Patients With Locally Advanced or Metastatic Bladder Urothelial Carcinoma

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.

Study Overview

• Status: Unknown
• Conditions: Bladder Urothelial Carcinoma
• Intervention / Treatment: Biological: humanized anti-PD-1 monoclonal antibody toripalimab

Detailed Description

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.The implementation of study meet the GCP.370 patients will be enrolled in the study to evaluate the safety and efficacy of JS001.Patients are injected with JS001 with 3mg/kg every 2 weeks until disease progresses or unacceptable toxicity occurs.Response assessment is conducted by every 8 weeks in first year, every 12 weeks in second year and every 16 weeks in third year and beyond.

• Study Type: Interventional
• Enrollment (Anticipated): 370
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Jun Guo, Phd; Md; Email: guoj307@126.com
      • Principal Investigator: Jun Guo, PhD; MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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;
• Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix.
• Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: humanized anti-PD-1monoclonal antibody; 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; 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.; Other Names: JS001, TAB001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR) by RECIST1.1 and irRECIST	The treatment effect of JS001 will be assessed using irRC and RECIST 1.1 to determine duration of response.	3 years
Progression free survival (PFS) by RECIST1.1 and irRECIST	The treatment effect of JS001 will be assessed using irRC and RECIST 1.1 to determine progression-free survival time.	3 years
Overall survival (OS)	The treatment effect of JS001 will be assessed using irRC and RECIST 1.1 to determine overall survival.	3 years
Immunogenicity of anti-PD-1 monoclonal antibody	To test immunogenicity of anti-PD-1 monoclonal antibody	3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation analysis of PD-L1 expression of tumor by ORR	correlation analysis of PD-L1 expression of tumor and objective response rate	3 years
Correlation analysis of PD-L1 expression of tumor by Immunohistochemistry	to analyse PD-L1 expression of tumor by Immunohistochemistry	3 years

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2017
• Primary Completion (Actual): March 15, 2020
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: April 9, 2017
• First Posted (Actual): April 13, 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: Advanced; Metastatic; Bladder Urothelial Carcinoma; anti-PD-1 monoclonal antibody
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: Junshi-JS001-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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