A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer

A Phase II Single Arm Clinical Trial of Nivolumab (BMS-936558) in Subjects With Metastatic or Unresectable Urothelial Cancer Who Have Progressed or Recurred Following Treatment With a Platinum Agent

The purpose the study is to measure the effect of nivolumab (BMS-936558) in reducing tumor size in subjects with metastatic or unresectable bladder cancer.

Study Overview

• Status: Completed
• Conditions: Various Advanced Cancer
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Local Institution - 0060
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Local Institution - 0070
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution - 0022
  • Edegem, Belgium, 2650
    • Local Institution - 0023
  • Hasselt, Belgium, 3500
    • Local Institution - 0024
• Czechia
  • Brno, Czechia, 656 53
    • Local Institution - 0027
  • Olomouc, Czechia, 779 00
    • Local Institution - 0026
  • Praha 5, Czechia, 150 06
    • Local Institution
• Finland
  • Helsinki, Finland, 00029
    • Local Institution - 0010
  • Tampere, Finland, 33521
    • Local Institution - 0009
• Germany
  • Erfurt, Germany, 99028
    • Local Institution - 0049
  • Erlangen, Germany, 91054
    • Local Institution - 0047
  • Hamburg, Germany, 20246
    • Local Institution - 0042
  • Heidelberg, Germany, 69120
    • Local Institution - 0043
  • Jena, Germany, 07747
    • Local Institution - 0015
  • Muenchen, Germany, 81675
    • Local Institution - 0041
  • Rostock, Germany, 18107
    • Local Institution
  • Tuebingen, Germany, 72076
    • Local Institution - 0048
• Italy
  • Arezzo, Italy, 52100
    • Local Institution - 0017
  • Milano, Italy, 20133
    • Local Institution - 0020
  • Napoli, Italy, 80131
    • Local Institution - 0018
  • Pavia, Italy, 27100
    • Local Institution - 0050
  • Roma, Italy, 00149
    • Local Institution - 0021
• Japan
  • Akita
    • Akita-shi, Akita, Japan, 0108543
      • Local Institution - 0074
  • Aomori
    • Hirosaki-shi, Aomori, Japan, 036-8563
      • Local Institution - 0083
  • Ibaraki
    • Tsukuba-shi, Ibaraki, Japan, 3058576
      • Local Institution - 0081
  • Iwate
    • Morioka-shi, Iwate, Japan, 0208505
      • Local Institution - 0078
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2360004
      • Local Institution
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 8608556
      • Local Institution - 0080
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • Local Institution - 0082
  • Niigata
    • Niigata-shi, Niigata, Japan, 9518520
      • Local Institution - 0076
  • Osaka
    • Osaka-Sayama-Shi, Osaka, Japan, 5898511
      • Local Institution - 0084
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138431
      • Local Institution - 0085
    • Bunkyo-ku, Tokyo, Japan, 1138603
      • Local Institution - 0073
    • Bunkyo-ku, Tokyo, Japan, 1138655
      • Local Institution - 0077
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Local Institution - 0086
    • Shinjuku-ku, Tokyo, Japan, 1628666
      • Local Institution - 0075
• Poland
  • Gdansk, Poland, 80-219
    • Local Institution
  • Krakow, Poland, 31-531
    • Local Institution - 0046
  • Lodz, Poland, 93-513
    • Local Institution - 0040
  • Szczecin, Poland, 71-730
    • Local Institution - 0056
  • Wroclaw, Poland, 50-556
    • Local Institution - 0038
• Spain
  • Badalona-barcelona, Spain, 08916
    • Local Institution - 0035
  • Barcelona, Spain, 08035
    • Local Institution - 0033
  • Hospitalet de Llobregat - Barcelona, Spain, 08908
    • Local Institution - 0034
  • Madrid, Spain, 28007
    • Local Institution - 0031
  • Sevilla, Spain, 41013
    • Local Institution - 0032
• Sweden
  • Lund, Sweden, 221 85
    • Local Institution - 0014
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Local Institution - 0013
  • California
    • Duarte, California, United States, 91010-3000
      • Local Institution - 0012
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0016
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer Blood Ctr
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Ft. Wayne Med Onco-Hema Inc
    • Indianapolis, Indiana, United States, 46202
      • Local Institution - 0030
  • Iowa
    • Iowa City, Iowa, United States, 55242
      • Local Institution - 0052
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Crescent City Research Consortium, LLC
  • Michigan
    • Detroit, Michigan, United States, 48201-2014
      • Karmanos Cancer Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • GU Research Network, LLC
  • New York
    • New York, New York, United States, 10029
      • Local Institution - 0028
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0004
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 0051
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2412
      • Local Institution - 0029
    • Pittsburgh, Pennsylvania, United States, 15212-0000
      • Local Institution - 0059
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Erlanger Oncology & Hematology - Univ. of TN
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 0001
  • Washington
    • Seattle, Washington, United States, 98101
      • Local Institution - 0036

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:

• Evidence of metastatic or surgically unresectable transitional cell carcinoma of the urothelium involving the bladder,urethra,ureter or renal pelvis
• Measurable disease by CT or MRI
• Progression or recurrence after treatment
• i) With at least 1 platinum-containing chemotherapy regimen for metastatic or surgically unresectable locally advanced urothelial cancer, or
• ii) Within 12 months of peri-operative (neo-adjuvant or adjuvant) treatment with a platinum agent in the setting of cystectomy for localized muscle-invasive urothelial cancer
• Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
• Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Exclusion Criteria:

• Subjects with active cancer that has spread to the central nervous system
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
• Subject with active, known or suspected autoimmune disease
• Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
• Prior treatment with an anti-PD-1,anti-PD-L1,anti-PD-L2,anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, anti-CD137 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways

Exclusion laboratory criteria:

• Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Known history of testing positive for human Immunodeficiency virus (HIV) or known acquired Immunodeficiency syndrome (AIDS)

Other protocol-defined inclusion/exclusion criteria apply

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: Nivolumab; Nivolumab intravenous infusion as specified	Drug: Nivolumab; Other Names: BMS(936558)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate Per BIRC Assessment	Objective Response Rate (ORR) was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee	From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months)
ORR Per BIRC Assessment by PD-L1 Expression Level	Objective Response Rate (ORR) was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee PD-L1 expression level= membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells. n = Number of participants in each category	From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months)
Time to Response (TTR)	TTR is defined as the time from first dosing date to the date of the first confirmed complete response (CR) or partial response (PR), as assessed by the Blinded Independent Review Committee (BIRC). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From first dosing date to the date of the first confirmed response (up to approximately 14 months)
Duration of Response (DOR)	DOR is defined as the time from first confirmed response, complete response (CR) or partial response (PR) to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment.	From the first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 14 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from first dosing date to the date of the first documented tumor progression, based on Blinded Independent Review Committee (BIRC) assessments or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PD-L1 expression level is defined as membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.	From first dosing date to the date of the first documented tumor progression (up to approximately 6 months)
Overall Survival (OS)	Overall Survival was defined as the time from first dosing date to the date of death. A participant who had not died was censored at last known date alive. PD-L1 expression level = membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.	From first dosing date to the date of death (up to approximately 23 months)
Objective Response Rate (ORR) Per Investigator	Investigator-assessed ORR was defined as the percent of participants with a best overall response of confirmed complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD-L1 expression level = Membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.	From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 45 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

General Publications

• Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, Plimack ER, Vaena D, Grimm MO, Bracarda S, Arranz JA, Pal S, Ohyama C, Saci A, Qu X, Lambert A, Krishnan S, Azrilevich A, Galsky MD. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):312-322. doi: 10.1016/S1470-2045(17)30065-7. Epub 2017 Jan 26.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2015
• Primary Completion (Actual): April 15, 2016
• Study Completion (Actual): November 12, 2021

Study Registration Dates

• First Submitted: February 26, 2015
• First Submitted That Met QC Criteria: March 12, 2015
• First Posted (Estimate): March 13, 2015

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209-275