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Safety, Tolerability, Pharmacokinetics, and Immunoregulatory Study of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

This study has been completed.
Information provided by (Responsible Party):
Bristol-Myers Squibb Identifier:
First received: November 10, 2011
Last updated: April 17, 2017
Last verified: August 2016
The purpose of the study is to assess the safety, tolerability, pharmacokinetics and immunoregulatory activity of urelumab (BMS-663513) in cancer subjects with advanced and/or metastatic tumors and relapsed/refractory B-Cell Non-Hodgkin's Lymphoma

Condition Intervention Phase
Cancer - Solid Tumors and B-Cell Non-Hodgkin's Lymphoma
Drug: Urelumab (BMS-663513)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Immunoregulatory Activity of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

Resource links provided by NLM:

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests [ Time Frame: Every 3 weeks from Baseline (Day 1) for up to 2 years ]
    The incidence of adverse events will be tabulated and reviewed for potential significance and clinical Importance.

  • Dose-limiting toxicity and maximum tolerated dose of Urelumab (BMS-663513) as determined by the incidence of dose-limiting toxicities [ Time Frame: Every 3 weeks from Baseline (Day 1) for up to 9 weeks of therapy ]

Secondary Outcome Measures:
  • Maximum observed serum concentrations (Cmax) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 ]
  • Minimum observed serum concentrations (Cmin) of Urelumab (BMS-663513) [ Time Frame: Cycle 2 Day 1, Cycle 3 Day 1, every 12 weeks thereafter up to 2 years ]
  • Time of maximum observed serum concentration (Tmax) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 ]
  • Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ]
  • Plasma half-life (T-HALF) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ]
  • Total body clearance (CLT) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ]
  • Volume of distribution at steady-state (Vss) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ]
  • Human Anti-human Antibodies [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ]
    Immunogenicity of Urelumab (BMS-663513), as determined by blood sample measurements of human antihuman antibodies (HAHA)

  • Tumor response and progression as determined by proportion of patients with best overall response (BOR), progression-free survival (PFS), objective response rate (ORR), time to response, and duration of response [ Time Frame: 9 weeks from Baseline (Day 1) and every 9 weeks until disease progression, death or last tumor assessment (Approximately up to 2 years) ]

Enrollment: 124
Study Start Date: February 2012
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 : Urelumab (BMS-663513) Dose escalation
Urelumab (BMS-663513) solution administered intravenously on specified days
Drug: Urelumab (BMS-663513)
Experimental: Part 2 : Urelumab (BMS-663513) Cohort Expansion
Urelumab (BMS-663513) solution administered intravenously on specified days
Drug: Urelumab (BMS-663513)
Experimental: Part 3:Urelumab (BMS-663513) Tumor-specific Cohort Expansions
Enrollment of subjects of three specific tumor types [(colorectal cancer (CRC), head and neck squamous cell carcinoma (SCCHN), and B-Cell non-Hodgkin's lymphoma (B-NHL)] who will be treated at the Maximum Tolerated Dose (MTD) (or highest dose tested)
Drug: Urelumab (BMS-663513)
Experimental: Part 4:Urelumab (BMS-663513) Cohort Expansion in B-NHL
Arm A and Arm B: Urelumab (BMS-663513) liquid administered intravenously on specified days exploring q3w and q6w dosing regimen
Drug: Urelumab (BMS-663513)


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

For more information regarding BMS clinical trial participation, please visit

Inclusion Criteria:

  1. Signed Written Informed Consent

    • The signed informed consent form
  2. Target Population

    • Subjects with advanced and/or metastatic solid tumors or B-NHL who are either refractory to or have relapsed from standard therapies, or for whom a standard therapy does not exist with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
    • Life expectancy of 12 weeks or greater
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
    • Adequate organ and marrow function
    • For certain subjects, willing and able to provide pre- and post-treatment fresh tumor biopsies
  3. Age and Reproductive Status

    • Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks prior to initiation of dosing, and for at least 60 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized
    • WOCBP must have a negative serum or urine pregnancy test [minimum sensitivity 25 UI/L or equivalent units of human chorionic gonadotrophin (HCG)] within 24 hours prior to the start of investigational product
    • Women must not be breastfeeding

Exclusion Criteria:

  1. Target Disease Exceptions

    • Subjects with known or suspected brain metastasis unless previously treated and without evidence of progression
    • Subjects with a history of prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured
    • Subjects with hepatocellular carcinoma
  2. Medical History and Concurrent Diseases

    • Any active autoimmune disease or documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo, psoriasis inactive within past 2 years, resolved childhood asthma/atopy, or thyroid disease controlled by replacement therapy without the need for immunosuppression
    • Known or suspected human immunodeficiency virus (HIV) or hepatitis A(acute), B or C infection
    • History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), drug-related, auto-immune)
    • Evidence of active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy < 7 days prior to administration of study medication
    • History of clinically significant cardiac disease, including but not limited to a history (personal or family) of congenital long QT syndrome
    • Grade > 1 QTc prolongation at baseline (> 450 msec by Bazett formula) confirmed by a repeat electrocardiogram (ECG)
    • History of myocardial infarction or uncontrolled angina within 12 months prior to administration of study drug
  3. Physical and Laboratory Test Findings

    • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product
    • Women who are pregnant or breastfeeding
    • Women with a positive pregnancy test on enrollment or prior to investigational product administration
    • Sexually active fertile men not using effective birth control if their partners are WOCBP
    • Positive blood screen for hepatitis A IgM, hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody
  4. Allergies and Adverse Drug Reaction

    • History of allergy to Urelumab (BMS-663513) or related compounds
    • History of significant drug allergy (such as anaphylaxis or hepatotoxicity) to a prior biologic therapy
  5. Prohibited Treatments and/or Therapies

    • The systemic use of the following therapies are prohibited within 28 days of first dose of study medication, or longer where indicated:

      1. Use of anti-cancer treatment (including investigational drugs) within 28 days
      2. Immunosuppressive medications or immunosuppressive doses of systemic corticosteroids
      3. Surgery (except minor surgeries,e.g., biopsies) or radiotherapy
      4. Any non-oncology live viral vaccine therapies used for the prevention of infectious diseases.
    • Prior treatment with anti-programmed death 1 (anti-PD-1)/Programmed cell death 1 ligand 1 (PD-L1) or anti-CD137
    • Any subject with the following reported drug-related adverse events on anti- Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) will not be permitted on study: hepatic, diarrhea/colitis or endocrine adverse events (AE)s Grade ≥ 2, any other non-laboratory immune-related AE ≥ Grade 3. Subjects must have minimum 9 week washout period between the last dose of anti-CTLA4 and the first dose Urelumab (BMS-663513)
    • Prior organ allograft or allogeneic bone marrow transplantation
  6. Other Exclusion Criteria

    • Prisoners or subjects who are involuntarily incarcerated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01471210

United States, California
Division Of Hematology & Oncology Ctr. For Health Sciences
Los Angeles, California, United States, 90095
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Illinois
University Of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New Jersey
John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Oregon
Providence Portland Med Ctr
Portland, Oregon, United States, 97213
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Hospital Of The University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
University Of Virginia Health System
Charlottesville, Virginia, United States, 22908
Local Institution
Creteil Cedex, France, 94010
Local Institution
Lille Cedex, France, 59037
Local Institution
Paris, France, 75475
Local Institution
Pessac, France, 33604
Local Institution
Pierre Benite Cedex, France, 69495
Local Institution
Rennes Cedex 9, France, 35033
Local Institution
Rouen, France, F-76038
Local Institution
Villejuif Cedex, France, 94805
Local Institution
Essen, Germany, 45147
Hospital Universitari Vall D'Hebron
Barcelona, Spain, 08035
Fundacion Jimenez Diaz
Madrid, Spain, 28040
Local Institution
Pamplona, Spain, 31192
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb Identifier: NCT01471210     History of Changes
Other Study ID Numbers: CA186-011
2012-000170-28 ( EudraCT Number )
Study First Received: November 10, 2011
Last Updated: April 17, 2017

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases processed this record on May 22, 2017