GlioblastomaPhase 1NCT04015700
Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma
A Phase 1 study testing Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics, CELLECTRA®2000 EP Device supplied by Geneos Therapeutics and Plasmid encoded IL-12 in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics, CELLECTRA®2000 EP Device supplied by Geneos Therapeutics and Plasmid encoded IL-12
- Type of treatment
- Vaccines, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2020to 26 Mar 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Systemic corticosteroid therapy is permitted provided dosing is no greater than 4 mg per day (dexamethasone or equivalent) on the day of vaccine administration.
- Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation, including at least 5 months (for women of childbearing potential) and at least 7 months (for men) after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- 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.
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- 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.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of first dose of vaccine.
- Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM injections
- Fewer than 2 acceptable sites available for IM injection and CELLECTRA® 2000 EP considering the deltoid and anterolateral quadriceps muscles:
- Tattoos, keloids, or hypertrophic scars located within 2 cm of intended administration site
- Implantable-cardioverter-defibrillator (ICD) or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist)
- Any metal implants or implantable medical device within the intended treatment site (i.e. electroporation area).
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Pilot Study to Assess the Safety, Feasibility, and Immunogenicity of a Neoantigen-based Personalized in Patients With Newly Diagnosed, Unmethylated Glioblastoma
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.
- Conditions
- Glioblastoma
- Being tested
- Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics, CELLECTRA®2000 EP Device supplied by Geneos Therapeutics, Plasmid encoded IL-12
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Personalized neoantigen DNA vaccine supplied by Geneos TherapeuticsBiological
Also called GNOS-PV01, Vaccine
-The neoantigen DNA vaccines are also known as DNA plasmid vector expressing tumor-specific antigens.
CELLECTRA®2000 EP Device supplied by Geneos TherapeuticsDevice
CELLECTRA® 2000 Device is a system indicated for use to enhance the uptake and expression of plasmid-based biologics in order to enhance vaccine efficacy.
Plasmid encoded IL-12Drug
Also called INO-9012
The INO-9012 vials will be supplied by Geneos Therapeutics
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics; Device: CELLECTRA®2000 EP Device supplied by Geneos Therapeutics; Drug: Plasmid encoded IL-12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of a Personalized Neoantigen DNA Vaccine as Measured by Number of Participants With Dose-limiting Toxicities (DLTs)
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
Measured: Up to 30 days
Feasibility of Generating a Personalized Neoantigen DNA Vaccine for Patients With Newly Diagnosed, Unmethylated GBM as Measured by the Number of Participants Who Had Candidate Tumor-specific Neoantigens Identified
The number of enrolled participants where at least one candidate tumor-specific neoantigen was identified for vaccine inclusion. Candidate neoantigen identification was done through tumor sequencing and in silico prediction algorithms prioritizing expressed (inferred by RNAseq) and presented (patient specific HLA class 1 molecule-restricted) peptides.
Measured: 4 weeks post-completion of radiotherapy (day 1 of cycle 1)
Feasibility of Generating a Personalized Neoantigen DNA Vaccine for Patients With Newly Diagnosed, Unmethylated GBM as Measured by the Number of Participants With a Manufactured Neoantigen-based DNA Vaccine
The number of enrolled participants with identifiable candidate tumor-specific neoantigen(s) who had a personalized DNA vaccine successfully manufactured.
Measured: 4 weeks post-completion of radiotherapy (day 1 of cycle 1)
Feasibility of Generating a Personalized Neoantigen DNA Vaccine for Patients With Newly Diagnosed, Unmethylated GBM as Measured by the Number of Participants Who Had the First Vaccine Administered at 4 Weeks Post-completion of Radiotherapy
The number of enrolled participants with identifiable candidate tumor-specific neoantigen(s) who had a personalized DNA vaccine successfully manufactured and administered by 4 weeks post-completion of radiation therapy.
Measured: 4 weeks post-completion of radiotherapy (estimated to be day 1 of cycle 1)
Secondary outcomes (8)
Immunogenicity of a Personalized Neoantigen DNA Vaccine as Measured by the Number of Participants With a Measurable Neoantigen-specific CD8 T Cell Response
CD8 T cells will be isolated from peripheral blood samples and will be stimulated with pooled peptides corresponding to the patient-specific neoantigen candidates included in the respective DNA vaccine. Response will be measured by IFN gamma production via ELISPOT assay.
Measured: Week 10 following vaccination on day 1 of cycle 1
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
CD8 T cells will be isolated from peripheral blood samples and will be stimulated with individual peptides corresponding to the patient-specific neoantigen candidates included in the respective DNA vaccine. Response will be measured by IFN gamma production via ELISPOT assay.
Measured: Week 10 following vaccination on day 1 of cycle 1
Number of High Quality Candidates Neoantigens Present in Participants With Newly Diagnosed GBM
-High quality neoantigens will be defined as those that meet criteria for inclusion in a vaccine
Measured: 4 weeks post-completion of radiotherapy (day 1 of cycle 1)
The Percentage of Participants Who Did Not Progress or Expire by 6 Months From Time of Diagnosis
-Progression is defined as any of the following
- ≥ 25% increase in sum products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline or best response, on stable or increasing doses of corticosteroids*. The absolute increase in any dimension must be at least 5mm when calculating the products.
- Significant increase in T2/FLAIR nonenhancing lesion on stable/increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events
- New measurable lesion.
- Clear clinical deterioration not attributable to other causes apart from the tumor (e.g. seizures, medication adverse effects, complications of therapy, cerebrovascular events, infection, and so on) or changes in corticosteroid dose.
Measured: 6 months
The Percentage of Participants Who Did Not Expire by 12 Months From Time of Diagnosis
Measured: 12 months
Immunogenicity of a Personalized Neoantigen DNA Vaccine as Measured by the Number of Participants That Had the T-cell Phenotype, Myeloid Derived Suppressor Cell Frequency by Flow Cytometry Analysis Performed
Measured: Up to week 24 post-vaccination (day 1 of cycle 1)
Immunogenicity of a Personalized Neoantigen DNA Vaccine as Measured by the Number of Participants That Had the Diversity of Clonality From T Cell Receptor Sequencing Analysis Performed
Measured by the number of patients that the analysis was able to be performed.
Measured: Up to week 24 post-vaccination (day 1 of cycle 1)
Immunogenicity of a Personalized Neoantigen DNA Vaccine as Measured by Putative Antigen Specificity From T Cell Receptor Sequencing
Measured: Up to week 24 post-vaccination (day 1 of cycle 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2019
- Study start14 Jul 2020
- Primary completion13 May 2022
- Study completion26 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Geneos Therapeutics, The Foundation for Barnes-Jewish Hospital, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Tanner M Johanns, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04015700
- Sponsor's protocol ID
- 202003072
- Other IDs
- R01NS112712
- Status last verified
- Oct 2026
- First submitted
- 8 Jul 2019
- Last updated
- 23 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Garfinkle EAR, Perales-Linares R, Gimple RC, Livingstone AJ, Roberts KF, Butt OH, Goedegebuure SP, McLellan MD, Chang GS, Hundal J, Yan J, Navarro JB, Paxton SA, Chattopadhyay S, Cooch N, Perales-Puchalt A, Stavroulaki K, Rochestie S, Peters J, Junker B, Campian JL, Chheda MG, Chicoine MR, Kim AH, Willie JT, Zipfel GJ, Dowling JL, Miller CA, Griffith OL, Griffith M, Gillanders WE, Miller KE, Mardis ER, Sardesai NY, Dunn GP, Johanns TM. Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial. Nat Cancer. 2026 Jul;7(7):1064-1079. doi: 10.1038/s43018-026-01163-w. Epub 2026 May 12.
PubMed 42120910