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

NCT ID: NCT03491683

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-31

Study Completion Date

2026-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Glioblastoma

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Glioblastoma immunotherapy DNA therapy checkpoint inhibitor

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cohort A: Unmethylated MGMT Promoter

Cohort 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.

Group Type EXPERIMENTAL

INO-5401

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

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

Intervention Type RADIATION

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

Intervention Type DRUG

Temozolomide (TMZ) will be given daily during radiation therapy (RT) at a dose of 75 milligrams per square meter (mg/m\^2).

Cohort B: Methylated MGMT Promoter

Cohort 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.

Group Type EXPERIMENTAL

INO-5401

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

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

Intervention Type RADIATION

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

Intervention Type DRUG

Temozolomide (TMZ) will be given daily during radiation therapy (RT) at a dose of 75 milligrams per square meter (mg/m\^2).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

INO-5401

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.

Intervention Type BIOLOGICAL

INO-9012

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.

Intervention Type BIOLOGICAL

Cemiplimab

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.

Intervention Type BIOLOGICAL

Radiation Therapy

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.

Intervention Type RADIATION

Temozolomide

Temozolomide (TMZ) will be given daily during radiation therapy (RT) at a dose of 75 milligrams per square meter (mg/m\^2).

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

REGN2810

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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).

* 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.

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;
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Inovio Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jeffrey Skolnik, MD

Role: STUDY_DIRECTOR

Inovio Pharmaceuticals

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope

Duarte, California, United States

Site Status

Stanford University, School of Medicine

Palo Alto, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Rutgers University - Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

New York University Langone Medical Center; Perlmutter Cancer Center

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Columbia University Medical Center The Neurological Institute of New York

New York, New York, United States

Site Status

New York-Presbyterian Hospital/Weill Cornell Medical Center

New York, New York, United States

Site Status

University of North Carolina School of Medicine

Chapel Hill, North Carolina, United States

Site Status

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Pennsylvania Health System: Penn Medicine

Philadelphia, Pennsylvania, United States

Site Status

UPMC Cancer Center Neuro-Oncology; UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, United States

Site Status

Texas Oncology

Austin, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

GBM-001

Identifier Type: -

Identifier Source: org_study_id