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

Status: Recruiting
Phase: Phase 1
Diagnosis: Cutaneous Skin Cancer
NCT ID: NCT01471210 (View complete trial on
DFCI Protocol ID: 12-161


The purpose of the study is to assess the safety, tolerability, pharmacokinetics and immunoregulatory activity of BMS-663513 in cancer subjects with advanced and/or metastatic tumors


Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital

Overall PI:
Frank Stephen Hodi, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Dana-Farber Cancer Institute: Suzanne MacRae, 617-632-5906,

Eligibility Criteria

Inclusion Criteria: 1. Signed Written Informed Consent - The signed informed consent form 2. Target Population - Subjects with advanced and/or metastatic solid tumors 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 - For all subjects, a tumor paraffin tissue block or 4-10 unstained slides from the tumor tissue block must be identified for biomarker analysis - Life expectancy of 12 weeks or greater - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 - Subjects must have failed, refused, or be unable to receive standard therapy for treatment of metastatic disease - Accessible and able to comply with treatment, pharmacokinetics (PK) and immune-monitoring sample collection and required study follow-up - Organ and marrow function as follows 1. Absolute neutrophil count ≥ 1,500 cells/mm3 2. Platelet count ≥ 100,000 cells/mm3 (transfusion to achieve this level is not permitted) 3. Hemoglobin ≥ 9.0 g/dL (transfusion to achieve this level is not permitted) 4. Total bilirubin < Institutional upper limit of normal (ULN) 5. Aspartate aminotransferase (ALT), Alanine aminotransferase (AST) < Institutional upper limit of normal (ULN) - Creatinine ≤ 1.5 times the ULN 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 3 weeks prior to initiation of dosing, and for at least 12 weeks 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 72 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 - Subjects with signs or symptoms suggestive of brain metastases are not eligible unless brain metastases are ruled out by computed tomography (CT) or Magnetic Resonance Imaging (MRI) - Subjects with a history of prior malignancy with the exception of nonmelanoma skin cancer, carcinoma in situ of the cervix, in situ carcinoma of the bladder, or other malignancy diagnosed > 5 years ago that has undergone potentially curative therapy with no evidence of disease for the last ≥ 5 years and that is deemed by the investigator to be a low risk for recurrence - Subjects with hepatocellular carcinoma 2. Medical History and Concurrent Diseases - History of autoimmune disease - 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 - Presence of underlying medical condition that in the opinion of the investigator or Sponsor could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy 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 - Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population - 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 BMS-663513 or related compounds - History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) 5. Prohibited Treatments and/or Therapies - Treatment with > 2 prior cytotoxic chemotherapy containing regimens for relapsed refractory cancer (agents such as interferon, interleukin 2, and vaccines would not be considered cytotoxic chemotherapy and would, therefore not count toward the total of 2 prior regimens) - 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 or at least 5 half-lives (whichever is longer) 2. Immunosuppressive agents 3. Surgery (except minor surgeries,e.g., biopsies) or radiotherapy 4. Systemic or inhalational corticosteroids. Ocular use of corticosteroids is permitted as is the transient use of topical corticosteroids over a limited surface area 5. Any non-oncology vaccine therapies used for the prevention of infectious diseases. The Gardasil vaccine also falls under this category since it is used to prevent Human Papillomavirus (HPV) 6. Growth factor treatment such as granulocyte-colony stimulating factor (G-CSF), or granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 28 days prior to first dose of study medication - 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 BMS-663513 - Prior organ allograft or allogeneic bone marrow transplantation 6. Other Exclusion Criteria - Prisoners or subjects who are involuntarily incarcerated - Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
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