Clinical trial NCT03491683: INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
Keywords: Glioblastoma
immunotherapy
DNA therapy
checkpoint inhibitor
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-04-09
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: 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:
measure: Overall survival at 18 months (OS18)
timeFrame: At Month 18
measure: Change from Baseline in Interferon-gamma Secreting T Lymphocytes in Peripheral Blood Mononuclear Cells (PBMCs)
timeFrame: From Day 0 to last dose of study treatment up to approximately 18 months
measure: Change from Baseline in T-Cell Phenotypes in PBMCs
timeFrame: From Day 0 to last dose of study treatment up to approximately 18 months
measure: Change from Baseline in T Cell Receptor (TCR) Subtypes in PBMCs
timeFrame: From Day 0 to last dose of study treatment up to approximately 18 months
measure: Change from Baseline in Antigen-Specific Humoral Response
timeFrame: From Day 0 to last dose of study treatment up to approximately 18 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Palo Alto
country: United States
facility: Stanford University, School of Medicine
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers University - Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: New York University Langone Medical Center; Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center The Neurological Institute of New York
state: New York
city: New York
country: United States
facility: New York-Presbyterian Hospital/Weill Cornell Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina School of Medicine
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System: Penn Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center Neuro-Oncology; UPMC Cancer Pavilion
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jeffrey Skolnik, MD
role: STUDY_DIRECTOR
References: