A Multicenter Trial to Identify Optimal Atezolizumab Biomarkers in the Setting of Recurrent Glioblastoma. The MOAB Trial

Recurrent glioblastoma represents one of the highest unmet medical needs in oncology. Overall prognosis remains poor for patients on standard of care therapies, with a 2-year survival rate of \< 20%. Immune checkpoint inhibitors have the potential to meet this unmet medical need, however such therapies have yet to be fully explored in clinical trials powered for efficacy nor in the neoadjuvant setting. The interplay between the immune system and glioblastoma is complex and shaped by a variety of factors. Certain molecular factors that suggest a promising response to immunotherapies, in non-CNS tumors, paradoxically indicate a worse response in glioblastoma. Atezolizumab has shown several properties that make it an ideal candidate for further investigation in rGBM. Interestingly, a low tumor mutational burden has been implicated in T cell inflammation and immunotherapy outcome in rGBM patients treated with atezolizumab. In this study, the investigators will determine whether neoadjuvant atezolizumab therapy provides a therapeutic benefit for patients with recurrent glioblastoma and a low mutational burden. Biological assessments of specimens collected in this trial will test the relationship between low TMB and features associated with immune-editing in rGBM. The investigators hypothesize that a low tumor mutational burden identifies immunologically engaged rGBM tumors and correlates with features previously linked to ICI response. By extensively studying the molecular factors influencing the response to immunotherapy, our goal is to enhance the effectiveness of immunotherapies in patients with glioblastoma.