Clinical trial
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)
Name
GBM-001
Description
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).
Trial arms
Trial start
2018-05-31
Estimated PCD
2023-12-31
Trial end
2023-12-31
Status
Active (not recruiting)
Phase
Early phase I
Treatment
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.
Arms:
Cohort A: Unmethylated MGMT Promoter, Cohort B: Methylated MGMT Promoter
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.
Arms:
Cohort A: Unmethylated MGMT Promoter, Cohort B: Methylated MGMT Promoter
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.
Arms:
Cohort A: Unmethylated MGMT Promoter, Cohort B: Methylated MGMT Promoter
Other names:
REGN2810
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.
Arms:
Cohort A: Unmethylated MGMT Promoter, Cohort B: Methylated MGMT Promoter
Temozolomide
Temozolomide (TMZ) will be given daily during radiation therapy (RT) at a dose of 75 milligrams per square meter (mg/m\^2).
Arms:
Cohort A: Unmethylated MGMT Promoter, Cohort B: Methylated MGMT Promoter
Size
52
Primary endpoint
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
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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 52, 'type': 'ACTUAL'}}
Updated at
2023-05-18
1 organization
4 products
1 indication
Product
INO-5401Indication
GlioblastomaOrganization
Inovio PharmaceuticalsProduct
TemozolomideProduct
INO-9012Product
Cemiplimab