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

Glioblastoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03491683
• Other study ID #: GBM-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 31, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Inovio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Biological:
• 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.
• 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.
• 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.

Radiation:
• 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.

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

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Texas Oncology	Austin	Texas
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Baylor College of Medicine	Houston	Texas
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Rutgers University - Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Columbia University Medical Center The Neurological Institute of New York	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	New York University Langone Medical Center; Perlmutter Cancer Center	New York	New York
United States	New York-Presbyterian Hospital/Weill Cornell Medical Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Stanford University, School of Medicine	Palo Alto	California
United States	University of Pennsylvania Health System: Penn Medicine	Philadelphia	Pennsylvania
United States	UPMC Cancer Center Neuro-Oncology; UPMC Cancer Pavilion	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Inovio Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival at 18 months (OS18)		At Month 18
Secondary	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
Secondary	Change from Baseline in T-Cell Phenotypes in PBMCs		From Day 0 to last dose of study treatment up to approximately 18 months
Secondary	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
Secondary	Change from Baseline in Antigen-Specific Humoral Response		From Day 0 to last dose of study treatment up to approximately 18 months