Clinical Trials /

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

NCT04015700

Description:

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.

Related Conditions:
  • Glioblastoma
  • Glioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma
  • Official Title: A Pilot Study to Assess the Safety, Feasibility, and Immunogenicity of a Neoantigen-based Personalized in Patients With Newly Diagnosed, Unmethylated Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: 18-x324
  • NCT ID: NCT04015700

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
Personalized neoantigen DNA vaccine supplied by Geneos TherapeuticsGNOS-PV01, VaccineVaccine (GNOS-PV01 + INO-9012)
Plasmid encoded IL-12INO-9012Vaccine (GNOS-PV01 + INO-9012)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Vaccine (GNOS-PV01 + INO-9012)ExperimentalStandard 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 for a total of 6 cycles or until intolerance or progression
  • Personalized neoantigen DNA vaccine supplied by Geneos Therapeutics
  • Plasmid encoded IL-12

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

          -  Presence of a cardioverter-defibrillator or pacemaker (to prevent a life-threatening
             arrhythmia) that is located ipsilateral to the intended deltoid injection site (unless
             deemed acceptable by a Cardiologist).

          -  Presence of any metal implants or implantable medical device within the
             electroporation area.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of a personalized neoantigen DNA vaccine as measured by dose-limiting toxicities (DLTs)
Time Frame:Up to 30 days
Safety Issue:
Description: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

Secondary Outcome Measures

Measure: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
Time Frame:Week 10 post-vaccination
Safety Issue:
Description:
Measure: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
Time Frame:Week 10 post-vaccination
Safety Issue:
Description:
Measure:Number of high quality candidates neoantigens present in patients with newly diagnosed GBM
Time Frame:Week 24 post-vaccination
Safety Issue:
Description:-High quality neoantigens will be defined as those that meet criteria for inclusion in a vaccine
Measure:Progression-free survival (PFS) rate
Time Frame:6 months
Safety Issue:
Description:PFS=duration of time from start of treatment to time of progression or death, whichever occurs first. Progression: 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 measureable 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.
Measure:Overall survival rate
Time Frame:12 months
Safety Issue:
Description:
Measure:Immunogenicity of a personalized neoantigen DNA vaccine as measured by T-cell phenotype, myeloid derived suppressor cell frequency by flow cytometry
Time Frame:Week 24 post-vaccination
Safety Issue:
Description:
Measure:Immunogenicity of a personalized neoantigen DNA vaccine as measured by diversity of clonality from T cell receptor sequencing
Time Frame:Week 24 post-vaccination
Safety Issue:
Description:
Measure:Immunogenicity of a personalized neoantigen DNA vaccine as measured by putative antigen specificity from T cell receptor sequencing
Time Frame:Week 24 post-vaccination
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

September 23, 2019