Phase 1b sitagliptin DPP-4 inhibitor + bevacizumab anti-VEGF mAb in recurrent grade 4 glioma

This Phase 1 trial tests repurposed sitagliptin (a small-molecule dipeptidyl peptidase-4 [DPP-4] inhibitor; Merck’s Januvia) combined with bevacizumab (a VEGF-A–neutralizing monoclonal antibody; Genentech/Roche’s Avastin) in adults with recurrent/progressive WHO grade 4 glioma (including recurrent glioblastoma). The core Phase 1b uses a standard 3+3 dose de-escalation to identify the maximum tolerated dose (MTD) of sitagliptin when given with bevacizumab in non-surgical patients, then a pilot “window-of-opportunity” cohort gives sitagliptin pre-operatively (≥5 days) at the MTD before tumor resection, followed by postoperative sitagliptin plus bevacizumab. The scientific angle is immune microenvironment modulation: the study is framed around targeting myeloid-derived suppressor cells (MDSCs), which are commonly enriched in glioblastoma and are associated with immunosuppression. For recurrent grade 4 glioma today, care is typically repeat surgery when feasible, re-irradiation in selected cases, and systemic options such as bevacizumab for symptom/radiographic control, nitrosoureas (e.g., lomustine), temozolomide rechallenge in select patients, and clinical trials—so this explores whether an inexpensive oral immunomodulatory add-on can improve outcomes or biomarkers beyond bevacizumab alone.