Data from Phase I Evaluation of Patients with Newly Diagnosed Glioblastoma Treated with Radiation, Nivolumab, and IDO1 Enzyme Inhibitor BMS-986205

<jats:p>&lt;div&gt;Abstract Purpose:&lt;p&gt;We conducted a phase I trial to evaluate radiotherapy (RT) and nivolumab with the further addition of an indoleamine 2,3-dioxygenase 1 (IDO1) enzyme inhibitor (BMS-986205) in newly diagnosed patients with glioblastoma (GBM) IDH wild-type.&lt;/p&gt; Patients and Methods:&lt;p&gt;In the current study, there were two primary cohorts of individuals. Cohort A included patients with O&lt;sup&gt;6&lt;/sup&gt;-methylguanine-DNA methyltransferase (MGMT)–unmethylated GBM who received RT with concurrent and adjuvant nivolumab with escalating BMS-986205 doses. Cohort B included patients with MGMT-methylated GBM who received BMS-986205 at 25 mg daily with RT, nivolumab, and temozolomide (TMZ) followed by adjuvant TMZ. Patient outcomes were correlated with flow cytometric, transcriptome, general metabolite, and microbial metabolite analyses.&lt;/p&gt; Results:&lt;p&gt;The treatments for both cohorts were moderately safe and tolerable. The treatment-emergent adverse events (TEAE) were mostly related to RT, TMZ, or the underlying disease and tumor progression. In cohort A, serious adverse events and TEAEs were predominantly lower grade, with no differences between the IDO1 enzyme inhibitor dosing cohorts. Dose-limiting toxicities reflected by increased transaminases (grade 3) were observed in two and three patients at the 50 and 100 mg levels of BMS-986205, respectively, with malaise observed in the 50 mg arm only. The 50 mg daily schedule was established as the recommended phase II dose (RP2D) in combination with RT and nivolumab. A number of exploratory correlative studies were also conducted.&lt;/p&gt; Conclusions:&lt;p&gt;This single-arm, small phase I trial establishes a safety profile and RP2D for RT in combination with nivolumab and BMS-986205 for newly diagnosed patients with MGMT-unmethylated GBM (ClinicalTrials.gov: NCT04047706).&lt;/p&gt;&lt;/div&gt;</jats:p>