Radiation Therapy With Temozolomide and Pembrolizumab in Treating Patients With Newly Diagnosed Glioblastoma

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of radiation therapy (RT) + temozolomide (TMZ) + MK-3475 (pembrolizumab) followed by MK-3475 + TMZ x 6 cycles (1 cycle is 9 weeks), MK-3475 can continue for an additional 12 months. SECONDARY OBJECTIVES: Safety of MK-3475 in GBM. TERTIARY OBJECTIVES: I. To determine if there is a correlation of programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PDL1) expression and T-cell infiltrate in pathology from first and, if applicable, second surgical specimens with outcome. II. Assess changes in peripheral T-cell activation and tryptophan metabolites. III. Correlate o-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) status with outcome. OUTLINE: This is a phase I, dose-escalation study of pembrolizumab, followed by a phase II study. RT PORTION: Patients undergo focal RT over 42 days, and receive concurrent temozolomide orally (PO) once daily (QD) on days 1-42 and pembrolizumab IV over 30 minutes on days 1, 22, and 43. POST-RT: After completion of RT, patients receive temozolomide PO QD on days 1-5 and 29-34 of course 1 and days 1-5 and 29-33 of subsequent courses, and pembrolizumab IV over 30 minutes on days 1, 22, and 43. Treatment repeats every 9 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients deriving benefit may continue to receive pembrolizumab for an additional 12 months. After completion of study treatment, patients are followed up every 2-4 months.