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vi20 NEURO-ONCOLOGY • NOVEMBER 2016 ATIM-11. PHASE 2 TRIAL OF SL-701, A NOVEL IMMUNOTHERAPY COMPRISED OF SYNTHETIC SHORT PEPTIDES AGAINST GBM TARGETS IL-13Rα2, EphA2, AND SURVIVIN, IN ADULTS WITH SECOND-LINE RECURRENT GBM: INTERIM RESULTS David  Reardon1, David  Peereboom2, Burt  Nabors3, Karen  Fink4, Surasak Phuphanich5, Tom Mikkelsen6, Erin Dunbar7, Michael Badruddoja8, David  Schiff9, Frank  Lieberman10, David  Tran11, Michael  Schulder12, Nicholas Butowski13, Lynn Ashby14, Christopher Moertel15, Fabio Iwamoto16, Jonathan Sherman17, Janice Chen18, Peter McDonald18, Enrique Poradosu18, Christopher  Brooks18, Shay  Shemesh18 and Jeffrey  Raizer19; 1Department of Neurooncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, 2Cleveland Clinic Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland, OH, USA, 3University of Alabama at Birmingham, Birmingham, AL, USA, 4Baylor University Medical Center/ Health Texas, Dallas, TX, USA, 5Neuro-Oncology Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA, 6Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA, 7Piedmont Brain Tumor Center, Atlanta, GA, USA, 8Center for Neurosciences, Tucson, AZ, USA, 9University of Virginia, Charlottesville, VA, USA, 10University of Pittsburgh Medical Center, Pittsburgh, PA, USA, 11Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL, USA, 12Hofstra Northwell School of Medicine, Manhasset, NY, USA, 13Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA, 14Barrow Neurological Institute, Phoenix, AZ, USA, 15University of Minnesota, Minneapolis, MN, USA, 16The Neurological Institute of New York, Columbia University, New York City, NY, USA, 17The George Washington University School of Medicine & Health Sciences, Washington, DC, USA, 18Stemine Therapeutics, Inc., New York, NY, USA, 19Northwestern University Feinberg School of Medicine, Chicago, IL, USA BACKGROUND: SL-701 is a novel immunotherapy comprised of synthetic short peptides designed to elicit an immune response against three overexpressed GBM targets: interleukin-13 receptor alpha-2 (IL-13Rα2), EphrinA2 (EphA2), and Survivin. We report preliminary data from an ongoing multicenter, 2-stage Phase 2 clinical trial of SL-701 in HLA-A2 positive adults with first recurrence of GBM. METHODS: Patients had to have KPS > 60, age > 18, and failed standard RT/TMZ. In Stage 1, SL-701 with adjuvants GM-CSF and imiquimod is administered biweekly for 6 months, then every 28 days thereafter. In Stage 2, SL-701 with the adjuvant poly-ICLC is administered biweekly with bevacizumab (10 mg/ kg). Primary objectives: 1) safety and tolerability 2) investigator assessed objective response rate (ORR) using RANO criteria and 3) survival rate at 12 months. RESULTS: As of 5/17/16, 58 patients (46 in Stage 1 and 12 in Stage 2) received SL-701. Accrual for Stage 1 is complete. Stage 2 accrual is ongoing. Median age is 55 years (range: 23–74), median KPS is 90, and 67% are male. Patients received a median of 4 doses. The most frequent grade 3–4 treatment-related adverse events (TRAEs) were fatigue (n = 1; 1.7%) and altered mental status (n = 1, 1.7%). Among 30 evaluable patients in Stage 1, there was 1 partial response (PR) (33+ weeks duration, ongoing) and 15 stable diseases (SD) (median duration: 8 weeks; range: 8–42+ weeks, ongoing). Of the 4 evaluable patients in Stage 2 to date, there has been 1 PR (8+ weeks duration, ongoing) and 3 SD (median duration: 8 weeks; range: 5–8+ weeks, ongoing). CONCLUSIONS: SL-701 plus adjuvants GM-CSF/ imiquimod or poly-ICLC and bevacizumab is well-tolerated. Patients are being followed for response, SD, PFS, and OS. Updated study data will be presented. ATIM-12. A METHOD TO CLASSIFY HUMAN ASTROCYTOMA CELL USING MULTIPARAMETRIC FLOW CYTOMETRY: A STEP TOWARDS SINGLE-CELL MOLECULAR PATHOLOGY OF SOLID TUMORS Rachel  Grossman1, Ilan  Volovitz1, Netanel  Shapira1 and Zvi  Ram2; 1Deaprtment of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel, 2The Neurosurgery Department, Tel Aviv Medical Center, Tel Aviv, Israel, Tel Aviv, Israel Multicolor flow cytometry (FCM) has revolutionized the molecular pathology of hematological tumors enabling multiparametric classification of single tumor cells. Meanwhile, the pathological evaluation of brain tumors (BTs) and other solid tumors, relies heavily on subjective histopathological evaluation of tissue slices stained for single antigens. To date, no FCM based method has been developed to classify human astrocytoma. METHODS: Human brain lesions were dissociated to single cells. The cells were analyzed using a five-color FCM staining panel concurrently monitoring Ki67 (a proliferation marker), GFAP (a glial marker) IL13 receptor a2 -IL13Ra2 (a glioma-associated antigen GAA), A2B5 (a GAA and a chemoresistance marker), and cellular viability. RESULTS: The Tumor-panel enabled blind classification of brain lesions to astrocytomas, to metastasis reaching the brain and to nontumorous lesions based on marker co-expression patterns consistent with the cells’ biology. The panel enabled quantification of the viable tumor cell fraction in lesions following enzymatic dissociation to single-cells and following a tumor-cell purification step using a density gradient. A clinically-relevant finding that emerged from the multiparametic analysis of antigen coexpression in gliomas was the partial coexpression of IL13Ra2 and Ki67: many Ki67+ (proliferating) cells did not express the IL13Ra2 GAA (i.e., IL13Ra2-Ki67+). This may partially explain the failure of several clinical trials that had targeted toxins to gliomas via IL13Ra2. CONCLUSIONS: FCM can be used to classify astrocytoma cells within single-cell dissociated brain lesions. The developed method represents a first step towards a quantitative, user-independent means for multiparametric classification and study of solid tumors. ATIM-13. PHASE I STUDY OF CHIMERIC ANTIGEN RECEPTORENGINEERED T CELLS TARGETING IL13Rα2 FOR THE TREATMENT OF GLIOBLASTOMA Christine  Brown1, Darya  Alizadeh2, Renate  Starr2, Lihong  Weng2, Jamie  Wagner2, Araceli  Naranjo2, Suzette  Blanchard2, Julie  Kilpatrick2, Jennifer  Simpson2, Julie Ann  Ressler2, Michael  Jensen3, Jana  Portnow2, Massimo D’Apuzzo2, Michael Barish4, Stephen Forman2 and Behnam Badie5; 1Dept Hematology-HCT / Medical Center / City of Hope, Duarte, CA, USA, 2City of Hope Comprehensive Cancer Center, Duarte, CA, USA, 3Seattle Children’s Research Institute, Seattle, WA, USA, 4Dept Devl Stem Cell Biol / Beckman Res Inst / City of Hope, Duarte, CA, USA, 5Department of Neurosurgery, City of Hope Comprehensive Cancer Center, Duarte, CA, USA T cell immunotherapy is emerging as a powerful strategy to treat cancer, and may offer opportunities to improve outcomes for patients with glioblastoma (GBM). We have optimized a chimeric antigen receptor (CAR) T cell therapy targeting the GBM-associated antigen IL13Rα2 that utilizes CD62L-enriched central memory T cells (Tcm) engineered by lentiviral transduction to express a second-generation 4-1BB-containing CAR (IL13BBζ). We report here initial findings from our first-in-human clinical trial [NCT02208362]. The aims of this trial include, (1) evaluation of the safety and feasibility of targeting IL13Rα2; and (2) comparison of intracranial delivery through intratumoral (with and without tumor resection) and intraventricular routes. To date, we have treated 10 patients and completed the first low-dose cohort of three resection patients. Local intracranial delivery of weekly IL13BBζ Tcm infusions has been safe and well-tolerated. Persisting CAR T cells were detected in the tumor cyst fluid or cerebral spinal fluid for a minimum of 7 days for patients with samples available. Evidence for CAR T cell bioactivity has been observed in a subset of patients, including decreased IL13Rα2 tumor antigen expression post-treatment. One patient of particular interest with recurrent multifocal GBM that included metastatic sites in the spine, was first treated with six weekly infusions of IL13BBζ Tcm into the resection cavity of the largest tumor, followed by ten weekly intraventricular infusions. In the absence of any other therapeutic interventions, this patient experienced a dramatic antitumor response with all intracranial and spinal tumors regressing 79%-97% by maximum area. This response was sustained for more than 7-months post-initiation of CAR T cell treatment. These early clinical findings suggest that intracranial delivery of second-generation IL13Rα2-targeted CAR T cells is safe and well-tolerated, and that CAR T cells are capable of eliciting potent antitumor responses against recurrent glioblastoma. ATIM-14. FIRST KOREAN EXPERIENCE OF DENDRITE CELLBASED IMMUNOTHERAPY IN PATIENTS WITH PRIMARY GLIOBLASTOMA Jaejoon  Lim and Kyung gi  Cho; Department of Neurosurgery, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, Republic of Korea OBJECTIVE: Dendritic cells are antigen presenting cells that recognize antigens and trigger an immune response in human immune system. Dendrite cell-based immunotherapy (DCI) has the potential to target and eliminate GBM cells. We evaluated the safety and efficacy of DCI in patients with primary glioblastoma. MATERIALS AND METHODS: The dendritic cells sensitized with self-tumor lysate, WT1 and KLH are intradermal injected on upper arm. We administrated the dendritic cells four times every two weeks and twice at intervals of two weeks after the 4weeks of rest period. We followed up patients two years. Treatment response was evaluated with CT and MRI, and immune response was evaluated with T cell proliferation assay and ELISPOT test. The Control group was set up to histological reference (newly diagnosed, standard treatment completed 24 patients). RESULTS: Thirteen patients received this immunotherapy. The total 83 related adverse events occurred. The eighty-tw

neuro-oncology

ATIM-11. PHASE 2 TRIAL OF SL-701, A NOVEL IMMUNOTHERAPY COMPRISED OF SYNTHETIC SHORT PEPTIDES AGAINST GBM TARGETS IL-13Rα2, EphA2, AND SURVIVIN, IN ADULTS WITH SECOND-LINE RECURRENT GBM: INTERIM RESULTS