ATIM-11. PILOT STUDY OF TUMOR LYSATE VACCINE AND IMIQUIMOD IN ADULTS WITH WHO GRADE II GLIOMAS

Abstract

BACKGROUND: We conducted a pilot study of intradermal vaccinations with tumor lysate and imiquimod in adults with newly diagnosed high-risk low-grade glioma (LGG). The vaccine uses the brain tumor initiating cell (BTIC) cell line GBM6-AD as antigen source. GBM6-AD expresses gliomaassociated antigens (GAAs), including interleukin-13 receptor (IL- 13R)α2, EphA2, and Her-2 and key BTIC antigens, including CD133, nestin, and Sox-2. METHODS: Patients were enrolled into three cohorts: LGG without prior therapy (Cohort 1); LGG with stable disease following chemo and /or radiation therapy (Cohort 2); or recurrent LGG (Cohort 3). Vaccinations were administered on weeks 0, 3, 9, 15 and 21 and every 16 weeks for up to 2 years. Imiquimod was applied topically prior to vaccination and at 24 hours. Primary endpoints were safety and CD8+ T-cell responses against vaccine targeted GAAs in post-vaccine PBMC using IFN-γ- ELISPOT. Exploratory endpoints were response and progression free survival (PFS). RESULTS: Cohorts 1, 2, and 3 enrolled 6, 11, and 2 patients, respectively. No regimen-limiting toxicity has been encountered. One patient died due to an accidental opioid overdose. There were one grade 4 lipase, and grade 3 AST and ALT elevation. Gr 1/2 fatigue was the most common AE in 7 patients. Other at least possibly related AE's (all grade 1) include seizure (3), injection site reaction (3), headache (2), decreased ANC (2) and one event of nausea, abdominal pain, fever and flu-like symptoms each. Best response was stable disease (n=18). Median PFS was 23.5 months (Cohort 1; since diagnosis; range 8-54 months) and 14 months (Cohort 3; since the 1st vaccine; range 8-28 months) and 14 months in cohort 3 (range 10-18 months). Sixteen patients are alive to date. CONCLUSIONS: The vaccine was well tolerated. Immunological and updated survival data will be presented. A larger efficacy study is warranted.