Ctim-06. Niacin Modulates Immune Responses in a Phase I Dose-Escalation Clinical Trial of Newly Diagnosed Glioblastoma

INTRODUCTION Immunotherapies such as immune checkpoint blockade have transformed cancer care in solid tumors such as melanoma, but have limited success in glioblastoma (GBM). GBM resists immunotherapies by fostering a profoundly immunosuppressive local microenvironment and altering systemic immunophenotypes. This involves decreasing CD4+ and CD8+ T cell and NK cell frequencies in the peripheral blood while expanding immunosuppressive myeloid subsets such as non-classical monocytes. In preclinical studies, we showed niacin (vitamin B3) administration ameliorates immunosuppression in the peripheral blood, alters leukocyte infiltration into the tumor, and improves outcomes. In this phase I trial, the objective is to determine whether niacin modulates systemic immunity in newly diagnosed GBM patients. METHODS This first-in-human phase I clinical trial (NCT04677049) investigates the immunomodulatory effects of oral controlled-release niacin (Niacin CRTTM) administered according to a dose escalation schedule (500-3,000mg daily) alongside standard of care surgery and chemoradiation in patients with newly diagnosed GBM. RESULTS Of the 15 patients enrolled, median age was 57 years and 60% were male. A gross total resection was achieved in 67% of patients, while 7% underwent biopsy only. Escalating niacin doses correlated with increasing frequencies of circulating memory T cells (p = 0.020) and natural killer cells (p = 0.027), while non-classical monocyte frequencies decreased (p = 0.019). Furthermore, niacin elevated serum levels of the pro-inflammatory cytokine interleukin (IL)-12p70 (p = 0.0078) and granulocyte colony-stimulating factor (G-CSF; p = 0.023), while reducing growth-regulated alpha protein (GROa; p = 0.039). DISCUSSION These data demonstrate that niacin exerts systemic immunomodulatory effects in GBM patients, shifting the immune landscape towards an anti-tumor profile and supporting further evaluation of niacin as a potential therapeutic adjunct. The promise of niacin as an adjunct is enhanced by its low-cost, accessibility, and established safety profile.