NCT04015700
Active, not recruiting
Phase 1
A Pilot Study to Assess the Safety, Feasibility, and Immunogenicity of a Neoantigen-based Personalized in Patients With Newly Diagnosed, Unmethylated Glioblastoma
Washington University School of Medicine1 site in 1 country9 target enrollmentStarted: July 14, 2020Last updated:
ConditionsGlioblastoma
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- Safety and tolerability of a personalized neoantigen DNA vaccine as measured by dose-limiting toxicities (DLTs)
Overview
Brief Summary
This is a single institution, open-label, single arm, study assessing the safety, feasibility, and immunogenicity of a personalized neoantigen-based vaccine in subjects with newly diagnosed, unmethylated glioblastoma.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Newly diagnosed histologically confirmed MGMT unmethylated glioblastoma multiforme (WHO grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded. High grade gliomas with molecular features of glioblastoma will be included. MGMT methylation status must be confirmed by standard a PCR-based assay.
- •Patients who had prior craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted.
- •Consent to genome sequencing and dbGaP-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/RNA samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done as part of routine care or another research project.)
- •At least 18 years of age.
- •Karnofsky performance status ≥ 60%
- •Normal bone marrow and organ function as defined below:
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelets ≥ 100,000/mcL
- •Total bilirubin ≤ 1.5 x IULN
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
Exclusion Criteria
- •As this study aims to assess the immunogenicity of personalized neoantigen DNA vaccine plus plasmid encoded IL-12 as an adjuvant, no prior immunotherapy will be permitted.
- •Inadequate tissue acquisition to allow for neoantigen screening.
- •No candidate neoantigen identified during screening.
- •A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy.
- •Receiving any other investigational agents within 4 weeks of beginning study treatment.
- •Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •History of immunodeficiency disorder or autoimmune condition requiring active immunosuppressive therapy. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines.
- •Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.
Arms & Interventions
Vaccine (GNOS-PV01 + INO-9012)
Experimental
- Standard radiation therapy will be administered per standard of care and is outside the scope of this study.
- GNOS-PV01 + INO-9012 will be given on Days 1, 22, and 43 of Cycle 1 and then on Day 1 of each subsequent cycle beginning with Cycle 2.
Intervention: Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics (Biological)
Vaccine (GNOS-PV01 + INO-9012)
Experimental
- Standard radiation therapy will be administered per standard of care and is outside the scope of this study.
- GNOS-PV01 + INO-9012 will be given on Days 1, 22, and 43 of Cycle 1 and then on Day 1 of each subsequent cycle beginning with Cycle 2.
Intervention: CELLECTRA®2000 EP Device supplied by Geneos Therapeutics (Device)
Vaccine (GNOS-PV01 + INO-9012)
Experimental
- Standard radiation therapy will be administered per standard of care and is outside the scope of this study.
- GNOS-PV01 + INO-9012 will be given on Days 1, 22, and 43 of Cycle 1 and then on Day 1 of each subsequent cycle beginning with Cycle 2.
Intervention: Plasmid encoded IL-12 (Drug)
Outcomes
Primary Outcomes
Safety and tolerability of a personalized neoantigen DNA vaccine as measured by dose-limiting toxicities (DLTs)
Time Frame: Up to 30 days
A DLT will be defined as any grade 3 toxicity or greater according to CTCAE v5 considered at least possibly related to study treatment. The DLT observation period begins with Cycle 1 Day 1 (date of first vaccine administration) and continues for 30 days
Feasibility of generating a personalized neoantigen DNA vaccine for patients with newly diagnosed, unmethylated GBM as measured by the ability to identify candidate tumor-specific neoantigens
Time Frame: 4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
Feasibility of generating a personalized neoantigen DNA vaccine for patients with newly diagnosed, unmethylated GBM as measured by the ability to manufacture a neoantigen-based DNA vaccine
Time Frame: 4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
Feasibility of generating a personalized neoantigen DNA vaccine for patients with newly diagnosed, unmethylated GBM as measured by the ability to administer the vaccine to a patient
Time Frame: 4 weeks post-completion of radiotherapy (day 1 of treatment regimen)
Secondary Outcomes
- Immunogenicity of a personalized neoantigen DNA vaccine as measured by T-cell phenotype, myeloid derived suppressor cell frequency by flow cytometry(Week 24 post-vaccination)
- Immunogenicity of a personalized neoantigen DNA vaccine as measured by putative antigen specificity from T cell receptor sequencing(Week 24 post-vaccination)
- Number of high quality candidates neoantigens present in patients with newly diagnosed GBM(Week 24 post-vaccination)
- Overall survival rate(12 months)
- Progression-free survival (PFS) rate(6 months)
- Immunogenicity of a personalized neoantigen DNA vaccine as measured by diversity of clonality from T cell receptor sequencing(Week 24 post-vaccination)
- Immunogenicity of a personalized neoantigen DNA vaccine as measured by the ability to generate a measurable neoantigen-specific CD8 T cell response in vaccinated patients(Week 10 post-vaccination)
- Immunogenicity of a personalized neoantigen DNA vaccine as measured by the number of individual neoantigens per number of neoantigens vaccinated against, with which a measurable CD8 T cell-specific response is identified(Week 10 post-vaccination)
Investigators
Study Sites (1)
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