This is a single institution, open-label, multi-arm, pilot study assessing the safety,
feasibility, and immunogenicity of a personalized neoantigen-based vaccine plus poly-ICLC
(NeoVax) combined with immune checkpoint inhibitors in subjects with newly diagnosed,
- Newly diagnosed histologically confirmed unmethylated glioblastoma multiforme (WHO
grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or
IDH2 mutant, will not be excluded. Unmethylated MGMT must be confirmed by a PCR-based
- Patients who had craniotomy with biopsy, subtotal resection, total gross resection, or
re-resection will be permitted.
- Consented 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 institutional upper limit of normal (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).
- As this study aims to assess the immunogenicity of various vaccine plus adjuvant
combinations, 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
- 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 poly-ICLC or other 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
- History of pre-existing immunodeficiency disorder or autoimmune condition requiring
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
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 7 days of first dose of vaccine.