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Trial record 28 of 1448 for:    glioblastoma

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

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ClinicalTrials.gov Identifier: NCT03491683
Recruitment Status : Active, not recruiting
First Posted : April 9, 2018
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Inovio Pharmaceuticals

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).

Condition or disease Intervention/treatment Phase
Glioblastoma Biological: INO-5401 Biological: INO-9012 Biological: Cemiplimab Radiation: Radiation Therapy Drug: Temozolomide Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 31, 2018
Estimated Primary Completion Date : January 18, 2021
Estimated Study Completion Date : January 18, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
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.

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.

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.
Other Name: REGN2810

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).

Experimental: 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.
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.

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.

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.
Other Name: REGN2810

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).




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Overall survival at 18 months (OS18) [ Time Frame: At Month 18 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Change from Baseline in Antigen-Specific Humoral Response [ Time Frame: From Day 0 to last dose of study treatment up to approximately 18 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03491683


Locations
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United States, California
City of Hope
Duarte, California, United States, 91010
Stanford University, School of Medicine
Palo Alto, California, United States, 94304
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Florida
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New Jersey
Rutgers University - Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, New York
New York University Langone Medical Center; Perlmutter Cancer Center
New York, New York, United States, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Columbia University Medical Center The Neurological Institute of New York
New York, New York, United States, 10032
New York-Presbyterian Hospital/Weill Cornell Medical Center
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina School of Medicine
Chapel Hill, North Carolina, United States, 27599
United States, Oklahoma
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania Health System: Penn Medicine
Philadelphia, Pennsylvania, United States, 19104
UPMC Cancer Center Neuro-Oncology; UPMC Cancer Pavilion
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Texas Oncology
Austin, Texas, United States, 78705
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Inovio Pharmaceuticals
Investigators
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Study Director: Jeffrey Skolnik, MD Inovio Pharmaceuticals

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Responsible Party: Inovio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03491683     History of Changes
Other Study ID Numbers: GBM-001
First Posted: April 9, 2018    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Inovio Pharmaceuticals:
Glioblastoma
immunotherapy
DNA therapy
checkpoint inhibitor

Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Cemiplimab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological