Anti-LAG-3 Alone & in Combination w/ Nivolumab Treating Patients w/ Recurrent GBM (Anti-CD137 Arm Closed 10/16/18)

PRIMARY OBJECTIVES: I. To determine a maximum tolerated dose or maximum administrated dose of anti-lymphocyte activation gene-3 (LAG-3) antibody (BMS-986016) (anti-LAG-3 monoclonal antibody BMS-986016) and anti-cluster of differentiation 137 (CD137) antibody (BMS- 663513) (urelumab) given independently and in combination with anti-programmed death-1 (PD-1) antibody (nivolumab, BMS-936558) safely in patients with recurrent glioblastoma multiforme (GBM). SECONDARY OBJECTIVES: I. To estimate overall survival. II. To estimate 1 year progression-free survival (PFS) rate. III. To estimate radiographic response (radiographic assessment in neuro-oncology \[RANO\] and immunotherapy response assessment for neuro-oncology \[iRANO\]). TERTIARY OBJECTIVES: I. To assess the pharmacodynamic effects of anti-LAG-3 antibody (BMS-986016), anti-CD137 antibody (BMS- 663513), and/or anti-PD-1 antibody (BMS-936558) on biomarkers in peripheral blood, including the T cell compartments, and serum proteins (cytokines and other immune modulators). II. To assess the pharmacodynamic activity in tumor tissue and peripheral blood in treated subjects who undergo optional tumor biopsies. III. To explore potential associations between biomarker measures and anti-tumor activity by analyzing markers of inflammation, immune activation, host tumor growth factors, and tumor-derived proteins in the pre-treatment and on-treatment setting. IV. To further characterize the occupancy and immune cell function at multiple dose levels of anti-LAG-3 antibody (BMS-986016), anti-CD137 antibody (BMS-663513), and/or anti-PD-1 antibody (BMS-936558). V. To explore characteristics of tumor immune microenvironment changes after the treatment of anti-LAG-3, anti-CD137, and its combination treatment with anti- PD-1 in surgically indicated patients undergoing tumor resection OUTLINE: PART A: This is a dose-escalation study of the monotherapy of Anti-LAG-3 monoclonal antibody BMS-986016 and Anti-CD137 (urelumab). Patients are assigned to 1 of 2 arms. ARM I: Patients receive anti-LAG-3 monoclonal antibody BMS-986016 intravenously (IV) on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive anti-CD137 (urelumab) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity. PART B: This is the dose-escalation combination therapy portion study of Anti-LAG-3 monoclonal antibody BMS-986016 plus Anti-PD-1(nivolumab) and Anti-CD137 (urelumab) plus Anti-PD-1 (nivolumab). Patients are assigned to 1 of 2 arms. ARM I: Patients receive Anti-PD-1 (nivolumab) IV over 60 minutes and anti-LAG-3 monoclonal antibody BMS-986016 IV on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive Anti-PD-1 (nivolumab) IV over 60 minutes on days 1 and 15 and urelumab IV on day 1. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. (2pts enrolled before the Anti-CD137 antibody (BMS-663513 - urelumab) treatment arm closed by BMS on 10/16/18 due to closure of BMS Urelumab development program. Subjects currently on treatment may continue.) INTRATUMORAL STUDIES: Patients enrolled on the Intratumoral Studies surgical arm pre-operatively receive either anti-LAG-3 monoclonal antibody BMS-986016 as in Part A Arm I, urelumab as in as in Part A Arm II, nivolumab and anti-LAG-3 monoclonal antibody BMS-986016 as in Part B Arm I, or nivolumab and urelumab as in Part B Arm II. Within 45 days of surgical resection, patients post-operatively receive either anti-LAG-3 monoclonal antibody BMS-986016 as in Part A Arm I, urelumab as in as in Part A Arm II, nivolumab and anti-LAG-3 monoclonal antibody BMS-986016 as in Part B Arm I, or nivolumab and urelumab as in Part B Arm II. (3pts enrolled before the Anti-CD137 antibody (BMS-663513 - urelumab) treatment arm closed by BMS on 10/16/18 due to closure of BMS Urelumab development program. Subjects currently on treatment may continue.) After completion of study treatment, patients are followed up at 60 days, every 2 months for 2 years, and then every 6 months thereafter. Patients taken off treatment for other reasons than disease progression are followed up every 2 months for 1 year.