ATIM-14. CMV gB/pp65 eVLPs FORMULATED WITH GM-CSF AS A THERAPEUTIC VACCINE AGAINST RECURRENT GLIOBLASTOMA (GBM). (5th November 2018)

• Record Type: Journal Article
• Authors: Iwamoto, Fabio; Diaz-Mitoma, Francisco; Anderson, David; Lassman, Andrew B
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi3
• Page End: vi3
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.009
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Cytomegalovirus (CMV) antigens have been reported in over 90% of GBM tumors. CD4 + and CD8 + T cells are most frequently directed against the highly immunogenic gB and pp65 antigens. We initiated a phase I/IIa clinical trial for patients with recurrent GBM using gB/pp65 enveloped virus-like particles (eVLPs) formulated with GM-CSF and administered intradermally. In phase I, eligible patients are age 18–70 with KPS at least 70, normal end-organ function, on stable or decreasing corticosteroids of at most 4mg dexamethasone (or equivalent), with recurrent GBM following any standard initial therapy and any number of recurrences. The primary endpoint is safety/tolerability, and secondarily to assess immunogenicity. Additional requirements for phase IIa designed to explore efficacy include unifocal, measurable enhancing tumor 1–3 cm across at first recurrence and no prior immunotherapy. Subjects are vaccinated monthly until tumor progression, with immunomonitoring performed 2 weeks after each vaccination. Up to 3 different vaccine doses will be evaluated, with 6 subjects in each cohort; ten additional subjects will be enrolled once an optimal vaccine dose is identified. To date, 6 patients were accrued 4 men, 2 women, median age 55 (range 39–66) in the first dose cohort. Prior therapies include radiotherapy, temozolomide, and nivolumab. No DLTs were observed. Dose level 1 (0.4µg pp65 content, 200µg GMCSF) is completed and dose Level 2 (2µg pp65 content) is currently accruing. Preliminary analysis of the first 4 subjects demonstrates boosting of CMV-specific antibody titers and T cell responses in two patients, associated with increases (2-3-fold) in plasma levels of CCL3 and proinflammatory INF-g and TNF-a cytokines. These two subjects remain clinically stable without tumor progression after approximately 4 months on study. An expanded immunomonitoring data set will be presented along with associated clinical responses of the subjects.