Atezolizumab and Cabozantinib for the Treatment of Recurrent Glioblastoma

PRIMARY OBJECTIVES: I. To evaluate the safety of atezolizumab in combination with cabozantinib. (Phase I) II. To evaluate the progression-free survival at six months (PFS-6) of atezolizumab in combination with cabozantinib. (Phase II) SECONDARY OBJECTIVE: I. To evaluate the progression free survival (PFS), overall survival (OS), overall response rate (ORR) and duration of response of atezolizumab in combination with cabozantinib. CORRELATIVE OBJECTIVES: I. Profiling tumor immune cell populations (i.e., macrophage migration inhibitory factor \[mIF\] and immunohistochemistry \[IHC\] analyses of CD4, CD8, PD1, PD-L1, and PD-L2 expression). II. Profiling of tumor, e.g., deoxyribonucleic acid (DNA), messenger (m) ribonucleic acid (RNA), microRNA and epigenetic profiling (DNA methylation), whole exome sequencing, RNA sequencing, and microRNA sequencing. III. Peripheral blood collection for evaluation of circulating chemokines/cytokines. IV. Stool collection for gut microbiome profiling. OUTLINE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 and cabozantinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then every 3 months thereafter.