INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM)

An Open-Label, Multi-Center Trial of INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With REGN2810 in Subjects With Newly-Diagnosed Glioblastoma (GBM)

Phase 1/2 trial to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with cemiplimab (REGN2810), with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM).

This is a phase 1/2, open-label, multi-center trial to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with cemiplimab in subjects with newly-diagnosed glioblastoma (GBM). INO-5401 and INO-9012 will be delivered by intramuscular (IM) injection followed by electroporation (EP) in combination with cemiplimab and chemoradiation and radiation. There will be 2 cohorts in this trial. Cohort A will be participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B will be participants with a tumor with a MGMT methylated promoter or who have indeterminate MGMT status. Both cohorts will receive INO-5401 and INO-9012 and cemiplimab at the same doses and on the same dosing schedule, and both cohorts will receive radiation and temozolomide (TMZ), if clinically indicated.

Inclusion Criteria:

• Newly-diagnosed brain cancer with histopathological diagnosis of GBM;
• Karnofsky Performance Status (KPS) rating of >/=70 at baseline;
• Receive dexamethasone equivalent dose </=2 mg per day, stable or decreased for >/= three days prior to Day 0;
• Recovery from the effects of prior GBM surgery as defined by the Investigator;
• Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator;
• Adequate organ function as demonstrated by hematological, renal, hepatic laboratory assessments;
• Agree that during the trial, men will not father a child, and women cannot be or become pregnant. Participants must be of non-child bearing potential or agree to use one highly effective or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and at least through week 12 after last dose;
• Ability to tolerate magnetic resonance imaging (MRI).

Exclusion Criteria:

• Presence of greater than 1 cm x 1 cm residual tumor enhancement on postoperative MRI;
• Multifocal disease or leptomeningeal disease (LM) disease on post-operative MRI;
• Not scheduled to start radiation within 42 days of surgical resection of tumor;
• Dexamethasone equivalent dose >2 mg per day;
• Prior treatment with an agent that blocks the PD-1/PD-Ligand 1 pathway;
• Receipt of previous approved or investigative immune modulatory agent within 28 days of receiving the first dose of treatment;
• Prior treatment with idelalisib;
• Past, current or planned treatment with tumor treatment fields; oncolytic viral treatment; or prior exposure to an investigational agent or device within 28 days of receiving the first dose of treatment;
• Allergy or hypersensitivity to cemiplimab or to any of its excipients;
• History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments;
• Ongoing or recent (within 5 years) evidence of autoimmune disease that required treatment with systemic immunosuppressive treatments;
• Diagnosis of immunodeficiency or treatment with systemic immunosuppressive therapy within 28 days prior to the first dose of trial treatment, other than dexamethasone for the underlying disease under investigation, as noted in the inclusion criteria;
• History of clinically significant, medically unstable disease which, in the judgment of the investigator, would jeopardize the safety of the subject, interfere with trial assessments or endpoint evaluation, or otherwise impact the validity of the trial results.