Clinical trial NCT01471210: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer - Solid Tumors and B-Cell Non-Hodgkin's Lymphoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-11-15
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

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

Primary outcomes:
measure: 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
timeFrame: Every 3 weeks from Baseline (Day 1) for up to 2 years
measure: Dose-limiting toxicity and maximum tolerated dose of Urelumab (BMS-663513) as determined by the incidence of dose-limiting toxicities
timeFrame: Every 3 weeks from Baseline (Day 1) for up to 9 weeks of therapy
Secondary outcomes:
measure: Maximum observed serum concentrations (Cmax) of Urelumab (BMS-663513)
timeFrame: Cycle 1 Day 1
measure: Minimum observed serum concentrations (Cmin) of Urelumab (BMS-663513)
timeFrame: Cycle 2 Day 1, Cycle 3 Day 1, every 12 weeks thereafter up to 2 years
measure: Time of maximum observed serum concentration (Tmax) of Urelumab (BMS-663513)
timeFrame: Cycle 1 Day 1
measure: Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of Urelumab (BMS-663513)
timeFrame: 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
measure: Plasma half-life (T-HALF) of Urelumab (BMS-663513)
timeFrame: 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
measure: Total body clearance (CLT) of Urelumab (BMS-663513)
timeFrame: 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
measure: Volume of distribution at steady-state (Vss) of Urelumab (BMS-663513)
timeFrame: 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
measure: Human Anti-human Antibodies
timeFrame: 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
measure: 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
timeFrame: 9 weeks from Baseline (Day 1) and every 9 weeks until disease progression, death or last tumor assessment (Approximately up to 2 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Division Of Hematology & Oncology Ctr. For Health Sciences
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Chicago
country: United States
facility: University Of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Portland Med Ctr
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital Of The University Of Pennsylvania
state: Pennsylvania
city: Charlottesville
country: United States
facility: University Of Virginia Health System
state: Virginia
city: Creteil Cedex
country: France
facility: Local Institution
city: Lille Cedex
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: Pierre Benite Cedex
country: France
facility: Local Institution
city: Rennes Cedex 9
country: France
facility: Local Institution
city: Rouen
country: France
facility: Local Institution
city: Villejuif Cedex
country: France
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Pamplona
country: Spain
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: