Phase II Trial Evaluating the Association of Peripheral Blood Immunologic Response to Therapeutic Response After Adjuvant Treatment with Immune Checkpoint Inhibition (ICI) in Patients with Newly Diagnosed Glioblastoma or Gliosarcoma.

Background: Glioblastoma (GBM) represents an aggressive malignancy with limited therapeutic options. The immunosuppressive nature of GBM may be reversible with immune checkpoint inhibitor (ICI) treatment, however, initial studies have yet to demonstrate this. It is postulated that trafficking of peripherally activated lymphocytes may play a role in generating a robust intracranial immune response. Therefore, a blood-based assay to identify peripheral blood response may both predict response and better identify the ideal patient populations for future ICI clinical trials. Methods: This was an open-label, Phase II, investigator-initiated exploratory study of patients with newly diagnosed GBM who completed maximal tumor resection and concurrent chemoradiation followed by standard adjuvant temozolomide and the combination of Nivolumab and Ipilimumab. The primary objective was to determine if the outcome, as measured by overall survival, is improved in patients when treatment with immune checkpoint inhibitors results in an immune response in peripheral blood T lymphocytes. The immune response is defined as changes in the CD4 Results: The study closed to enrollment early due to a shift in clinical priorities after the accrual of 40 patients. Twenty-three patients have died of their disease, and adequate samples for the primary analysis were available for 17 of these patients. The median OS for the 17 patients was 19 months (range 9-45months). For the four immune measurements, patients were categorized as Conclusion: In this limited cohort, no detectable difference in the OS was observed between patients with a