LAUSR

Despite advances in therapy, glioblastoma (GBM) remains one of the most deadly cancers, with five-year survival under 5%. Newer immunotherapies hold promise in the treatment of GBM, and T cell-enabling therapies may improve progression-free and overall survival for newly-diagnosed patients. Checkpoint inhibitors, such as PD-1 inhibitors, have increased response rates in many cancers, but not yet in GBM. In this study, a novel antigen-specific T cell-generating therapy, INO-5401, combined with INO-9012, together with a PD-1 checkpoint inhibitor, cemiplimab, will be given to patients with newly-diagnosed GBM in order to evaluate tolerability, immunogenicity and any activity of the combination. INO-5401 is a mixture of three synthetic plasmids that target Wilms tumor gene-1 (WT-1) antigen, prostate specific membrane antigen (PSMA), and human telomerase reverse transcriptase (hTERT) antigen. INO-9012 is a plasmid encoding human interleukin-12 (IL-12) p35 and p40 subunit proteins. In preclinical studies, targeting WT-1, PSMA and hTERT induced robust cellular immune responses and slowed tumor growth in murine tumor implantation and ALL models. This is a Phase I/IIA, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of INO-5401 + INO-9012 delivered by intramuscular (IM) injection followed by electroporation (EP), in combination with cemiplimab, and radiation and chemotherapy, in participants with newly-diagnosed GBM. INO-5401 + INO-9012 will be administered Q3w for the first four doses, and then Q9w until disease progression. Cemiplimab will be administered Q3w until disease progression. The trial population is divided into two cohorts: Cohort A are patients with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter; and Cohort B are patients with a methylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Both cohorts will receive radiation and temozolomide (TMZ), if clinically indicated, in combination with study therapies. Cohort B will continue TMZ for a total of 6 cycles. A safety run-in will be performed with up to six participants (safety analysis participants) from Cohort A and Cohort B. Correlative studies include the assessment of antigen-specific cellular immune responses in peripheral blood and tumor tissue. Fifty-two patients are estimated to be enrolled, 32 in Cohort A and 18 in Cohort B. Enrollment began in May of 2018 and the trial is continuing to accrue as planned. Citation Format: David Reardon, Seema Nagpal, Scott Soltys, Steven Brem, Antonio Omuro, Macarena De La Fuente, Amy-Lee Bredlau, Isreal Lowy, Matthew Fury, Matthew Morrow, Kim Kraynyak, Trevor McMullan, Ashley L. Santo, Brian Sacchetta, Jeffrey Skolnik. INO-5401 and INO-9012 delivered by electroporation (EP) in combination with cemiplimab (REGN2810) in newly-diagnosed glioblastoma (GBM) (NCT03491683) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT114.