Therabiome-gbm: therapeutic outcomes related to gut microbiome in glioblastoma (gbm) patients receiving chemo-radiation: a prospective observational study

Abstract PURPOSE A major barrier to improving outcomes in glioblastoma multiforme (GBM) is overcoming a heavily immunosuppressed tumor and systemic environment, as demonstrated by several negative phase III randomized studies of nivolumab in both newly diagnosed and recurrent GBM. In several mouse avatar and human studies across several tumor cohorts including in a humanized microbiome GBM model, re-establishing a new gut microbiome (GM) via fecal transplantation led to tumor responses to PD-1/PD-L1 inhibition. A recent scoping review confirmed a paucity of GM clinical data of a uniform GBM cohort with adequate longitudinal GM sample collection. We are conducting a single-center prospective observational study to establish the feasibility of collecting stool samples throughout the time course of GBM treatment and upon recurrence, and to understand the gut microbiome dynamics of newly diagnosed IDH-wild type (WT) GBM patients. METHODS Patients with newly diagnosed unifocal IDH-1 R132H WT WHO grade 4 GBM, ECOG 0-2, at least 70% tumor resected with plan to receive temozolomide-radiation (TMZ-RT) and adjuvant TMZ +/- Tumor Treating Fields are eligible. Stool samples will be collected prior to TMZ-RT, 4 weeks after TMZ-RT, after adjuvant TMZ, and upon recurrence. The primary endpoint is feasibility, defined as stool sample obtained pre-RT, post-RT (pre-adjuvant TMZ), and at time of recurrence in ≥ 70% of enrolled participants, 75% of target sample size enrolled within 2 years, and stool sample volume and quality sufficient for analysis in ≥ 75% of collected samples. Secondary endpoints include progression-free survival (PFS) in pre-defined GM subgroups, GM taxonomy and diversity in late vs. early progressors, and GM differences in patients with and without post-RT necrosis. Age, sex, race, concurrent medication, corticosteroid use, and diet will be carefully accounted for. Patient reported outcomes using EORTC-QLQ-BN20 and QLQ-C30 will be collected at baseline, 3-, 6-, 9-, and 12-months.