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

• ClinicalTrials.gov Identifier: NCT03491683
• Recruitment Status: Active, not recruiting
• First Posted: April 9, 2018
• Last Update Posted: May 18, 2023
• Sponsor: Inovio Pharmaceuticals
• Information provided by (Responsible Party): Inovio Pharmaceuticals

Tracking Information

• First Submitted Date: April 2, 2018
• First Posted Date: April 9, 2018
• Last Update Posted Date: May 18, 2023
• Actual Study Start Date: May 31, 2018
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 2, 2018): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 2, 2018)

• Overall survival at 18 months (OS18) [ Time Frame: At Month 18 ]
• 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 ]
• 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 ]
• 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 ]
• Change from Baseline in Antigen-Specific Humoral Response [ Time Frame: From Day 0 to last dose of study treatment up to approximately 18 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.
• 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).

Study Arms

• 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.
  Interventions:

  • Biological: INO-5401
  • Biological: INO-9012
  • Biological: Cemiplimab
  • Radiation: Radiation Therapy
  • Drug: Temozolomide
• 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.
  Interventions:

  • Biological: INO-5401
  • Biological: INO-9012
  • Biological: Cemiplimab
  • Radiation: Radiation Therapy
  • Drug: Temozolomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 2, 2018): 52
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03491683
• Other Study ID Numbers: GBM-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Inovio Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Inovio Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jeffrey Skolnik, MD; Inovio Pharmaceuticals

• PRS Account: Inovio Pharmaceuticals
• Verification Date: May 2023