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)
1 other identifier
interventional
52
1 country
21
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2018
Longer than P75 for phase_1
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 2, 2018
CompletedFirst Posted
Study publicly available on registry
April 9, 2018
CompletedStudy Start
First participant enrolled
May 31, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
May 4, 2026
May 1, 2026
8.6 years
April 2, 2018
May 1, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants with Adverse Events (AEs)
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
Secondary Outcomes (5)
Overall survival at 18 months (OS18)
At Month 18
Change from Baseline in Interferon-gamma Secreting T Lymphocytes in Peripheral Blood Mononuclear Cells (PBMCs)
From Day 0 to last dose of study treatment up to approximately 18 months
Change from Baseline in T-Cell Phenotypes in PBMCs
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
From Day 0 to last dose of study treatment up to approximately 18 months
Change from Baseline in Antigen-Specific Humoral Response
From Day 0 to last dose of study treatment up to approximately 18 months
Study Arms (2)
Cohort A: Unmethylated MGMT Promoter
EXPERIMENTALCohort A will include participants with a glioblastoma tumor with an unmethylated MGMT promoter. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ; only during radiation therapy), if clinically indicated.
Cohort B: Methylated MGMT Promoter
EXPERIMENTALCohort B will include participants with a glioblastoma tumor with a methylated MGMT promoter or with indeterminate MGMT status. Participants will receive INO-5401 and INO-9012 and cemiplimab as well as radiation and temozolomide (TMZ), if clinically indicated. Participants will continue to receive TMZ following radiation therapy, for up to six additional cycles, if clinically indicated.
Interventions
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.
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).
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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;
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
City of Hope
Duarte, California, 91010, United States
Stanford University, School of Medicine
Palo Alto, California, 94304, United States
University of California, San Francisco
San Francisco, California, 94143, United States
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University School of Medicine
Atlanta, Georgia, 30322, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Rutgers University - Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
New York University Langone Medical Center; Perlmutter Cancer Center
New York, New York, 10016, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Columbia University Medical Center The Neurological Institute of New York
New York, New York, 10032, United States
New York-Presbyterian Hospital/Weill Cornell Medical Center
New York, New York, 10065, United States
University of North Carolina School of Medicine
Chapel Hill, North Carolina, 27599, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
University of Pennsylvania Health System: Penn Medicine
Philadelphia, Pennsylvania, 19104, United States
UPMC Cancer Center Neuro-Oncology; UPMC Cancer Pavilion
Pittsburgh, Pennsylvania, 15232, United States
Texas Oncology
Austin, Texas, 78705, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Jeffrey Skolnik, MD
Inovio Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 2, 2018
First Posted
April 9, 2018
Study Start
May 31, 2018
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
May 4, 2026
Record last verified: 2026-05