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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
52
INO-5401 is a combination of 3 separate DNA plasmids targeting Wilms tumor gene-1 (WT1) antigen, prostate-specific membrane antigen (PSMA) and human telomerase reverse transcriptase (hTERT) genes. Starting on Day 0 three milligrams (mg) of each plasmid will be delivered IM followed by EP using the CELLECTRA® 2000 EP device every three weeks for four doses, and then every 9 weeks until disease progression as defined by immunotherapy Response Assessment in Neuro-Oncology (iRANO), unacceptable toxicity, withdrawal of consent, or death.
INO-9012 is a DNA plasmid for expression of human interleukin-12 (IL-12). Starting on Day 0 one mg plasmid will be delivered IM followed by EP using the CELLECTRA® 2000 EP device every three weeks for four doses, and then every 9 weeks until disease progression as defined by iRANO, unacceptable toxicity, withdrawal of consent, or death.
City of Hope
Duarte, California, United States
Percentage of Participants with Adverse Events (AEs)
Time frame: From Day 0 to 30 days after the last dose of study treatment (non-serious AEs) and to 6 months after the last dose of study treatment (immune-related AEs, AEs of special interest and serious AEs) up to approximately 24 months
Overall survival at 18 months (OS18)
Time frame: At Month 18
Change from Baseline in Interferon-gamma Secreting T Lymphocytes in Peripheral Blood Mononuclear Cells (PBMCs)
Time frame: From Day 0 to last dose of study treatment up to approximately 18 months
Change from Baseline in T-Cell Phenotypes in PBMCs
Time frame: From Day 0 to last dose of study treatment up to approximately 18 months
Change from Baseline in T Cell Receptor (TCR) Subtypes in PBMCs
Time frame: From Day 0 to last dose of study treatment up to approximately 18 months
Change from Baseline in Antigen-Specific Humoral Response
Time frame: From Day 0 to last dose of study treatment up to approximately 18 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Cemiplimab is an antibody to programmed death-1 (PD-1) protein. Starting on Day 0 cemiplimab will be administered intravenously (IV) every three weeks at a dose of 350 mg per dose in the absence of dose holding, until disease progression as defined by iRANO, unacceptable toxicity, withdrawal of consent, or death.
Radiation therapy (RT) will begin no later than 42 days after surgical intervention, and should start approximately 2 weeks after Day 0. RT will be given for three weeks.
Temozolomide (TMZ) will be given daily during radiation therapy (RT) at a dose of 75 milligrams per square meter (mg/m\^2).
Stanford University, School of Medicine
Palo Alto, California, United States
University of California, San Francisco
San Francisco, California, United States
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University School of Medicine
Atlanta, Georgia, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Henry Ford Health System
Detroit, Michigan, United States
Rutgers University - Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
New York University Langone Medical Center; Perlmutter Cancer Center
New York, New York, United States
...and 11 more locations