Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma

NCT ID: NCT04015700

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-14
• Study Completion Date: 2025-12-31

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.

Conditions

Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vaccine (GNOS-PV01 + INO-9012)

• 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.

Group Type: EXPERIMENTAL

Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics

Intervention Type: BIOLOGICAL

-The neoantigen DNA vaccines are also known as DNA plasmid vector expressing tumor-specific antigens.

CELLECTRA®2000 EP Device supplied by Geneos Therapeutics

Intervention Type: DEVICE

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-12

Intervention Type: DRUG

The INO-9012 vials will be supplied by Geneos Therapeutics

Interventions

Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics

-The neoantigen DNA vaccines are also known as DNA plasmid vector expressing tumor-specific antigens.

Intervention Type: BIOLOGICAL

CELLECTRA®2000 EP Device supplied by Geneos Therapeutics

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.

Intervention Type: DEVICE

Plasmid encoded IL-12

The INO-9012 vials will be supplied by Geneos Therapeutics

Intervention Type: DRUG

Other Intervention Names

GNOS-PV01; Vaccine; INO-9012

Eligibility Criteria

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
• 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).

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.
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Geneos Therapeutics

INDUSTRY

Sponsor Role: collaborator

The Foundation for Barnes-Jewish Hospital

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tanner M Johanns, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

202003072

Identifier Type: -

Identifier Source: org_study_id