The early clinical development paradigm for chemotherapeutic agents has significantly
influenced the development of therapeutic cancer vaccines. However, there are major
differences between these two classes of therapeutics that have important implications for
early clinical development. Specifically, the phase 1 concept of dose escalation to find a
maximum-tolerated dose does not apply to most therapeutic cancer vaccines. Most therapeutic
cancer vaccines are associated with minimal toxicity at a range that is feasible to
manufacture or administer, and there is little reason to believe that the maximum-tolerated
dose is the most effective dose.
In a recent article from the biostatistics literature, Simon et al. write that "the initial
clinical trial of many new vaccines will not be a toxicity or dose-ranging trial but rather
will involve administration of a fixed dose of vaccine … in most cases the dose selected will
be based on preclinical findings or practical considerations. Using several dose levels in
the initial study to find the minimal active dose or to characterize the dose-activity
relationship is generally not realistic".
Consistent with these recommendations, the general philosophy of the phase 1 clinical trial
is to facilitate a prompt preliminary evaluation of the safety and immunogenicity of the
personalized synthetic long peptide vaccine strategy. The proposed clinical trial will test a
fixed dose of vaccine. There is considerable experience with the synthetic long peptide
vaccine platform. The synthetic long peptide vaccine platform has an excellent safety
profile, and the optimal dose appears to be based on practical considerations (solubility of
the peptide). The dose to be tested in the proposed clinical trial is consistent with other
similar cancer vaccine trials that have been recently completed or are currently ongoing. The
sample size (n=10) will provide a reasonably reliable estimate of the safety and
immunogenicity of the vaccine.
- Newly diagnosed histologically confirmed glioblastoma multiforme (WHO grade IV).
Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant,
will not be excluded.
- 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 under
this study or 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. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she must inform her treating physician
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
- As this is a safety and feasibility study, prior immunotherapy will be permitted.
However, any prior immunotherapy must be discontinued at least 2 weeks before peptide
vaccine administration. Non-immunologic therapy may be continued.
- 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.
- Currently receiving any other investigational agents.
- 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 including chronic infection (i.e.
hepatitis B, hepatitis C, HIV), 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, Sjogren'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
- 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.