Phase 1b/2a study evaluating the combination of MN-166 (ibudilast) and temozolomide in patients with newly diagnosed and recurrent glioblastoma (GBM).

• DOI: 10.1200/jco.2024.42.16_suppl.2016
• Publication Date: 2024-06-04T19:02:17Z
• Authors: Gilbert Youssef; Justin Lathia; Eudocia Quant Lee; Ugonma Nnenna Chu...; Adam Lauko; Tracy Batchelor; Elisa Aquilanti; Lakshmi Nayak; Alexa Myers; Alyssa Russ; Catharina C Weste...; Tyler Alban; Jakub Jarmula; Juyeun Lee; Michael A. Vogelbaum; Kazuko Matsuda; David A. Reardon; Patrick Y. Wen
• Keywords: Temozolomide

2016 Background: Ibudilast is a selective inhibitor of macrophage inhibitory factor (MIF) activity, which upregulated in GBM and promotes stem cell growth. It also disrupts the interaction between MIF CD74. When combined with temozolomide (TMZ) preclinical studies, it attenuates immunosuppressive properties myeloid-derived suppressor cells enhances tumor regression. This phase 1b/2a single-center, open-label, dose escalation study evaluating safety, tolerability, efficacy combination TMZ newly diagnosed (nGBM) recurrent (rGBM) was initiated (NCT03782415). Methods: We included patients nGBM who had completed concurrent chemoradiation, first relapse measurable enhancing disease. Patients were treated monthly cycles (5 days 28-day cycle) daily ibudilast, starting 30 mg twice (BID), escalated to maximal 50 BID. The primary objectives evaluate safety tolerability determine 2 recommended (R2PD) for 1b, combination, determined by 6-month progression-free survival rate (PFS-6) 2a. A standard 3+3 design used 1b. For rGBM cohort, sample size provided 80% power discriminate historical 15% 35% PFS-6 rates patients. trial would be considered successful if at least 8 progression free 6 months. Secondary overall (OS). Immunohistochemistry (IHC) studies performed on archival samples factors immune microenvironment. Results: 36 26 included; 61% males, median age 59 years. BID deemed R2PD. 44% (16 patients) nGBM, 31% (8 rGBM. OS 21.0 months (17.7, 23.1) 8.6 (7.8, 10.5) IHC evaluation original tissue revealed significantly higher CD3 positive infiltration, elevated CD74 expression tumors progressed 5 compared those did not. Conclusions: met its endpoint rGBM, as ibudilast associated than controls. good predictor Encouraging suggest enhanced when checkpoint blockade agents. Clinical information: NCT03782415 .