Safety and Efficacy Study of SL-701, a Glioma-Associated Antigen Vaccine To Treat Recurrent Glioblastoma Multiforme

Inclusion Criteria: * 18 years of age or older. * Histologically confirmed GBM or World Health Organization (WHO) Grade IV variants (gliosarcoma, glioblastoma with oligodendroglial features, or giant cell glioblastoma). * Unequivocal evidence of a first tumor recurrence or progression on the initial treatment regimen (prior to enrollment on this study), consisting of surgical intervention (biopsy and/or resection), radiation, and temozolomide chemotherapy, as assessed by MRI or CT scan of the brain with or without contrast within 14 days prior to the start of SL-701. If receiving corticosteroids, the dose must be stable or decreasing for at least 5 days prior to the scan. Participants unable to undergo MRI because of non-compatible devices can be enrolled, provided CT scans are obtained and are of sufficient quality. For each participant, the same imaging technique should be performed throughout the study, for purposes of assessing tumor response or PD. * For participants who have undergone resection of recurrent or progressive tumor prior to study enrollment, the following conditions must apply: * Recovery from the effects of surgery. * Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, an MRI should be performed: * No later than 96 hours (h) in the immediate post-operative period; or * At least 4 weeks post-craniotomy (7 days for stereotactic biopsy), within 14 days prior to the start of SL-701, and on a corticosteroid dosage that has been stable or decreasing for at least 5 days. * Participants who have not had resection of recurrent or progressive disease must have measurable disease. * At least 56 of the approximately 76 participants treated must have measurable disease, defined as at least one, contrast-enhancing lesion measuring at least 1 cm in 2 planes (axial, coronal, or sagittal). * No evidence of hemorrhage on the baseline MRI or CT scan other than those that are Grade ≤ 1 and either post-operative or stable on at least two consecutive scans. * Recovery from prior therapy toxicity, defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia and lymphopenia). * At least 12 weeks from prior radiotherapy to the start of SL-701 unless there is new enhancement outside of the radiation field or unequivocal histopathologic evidence of recurrent tumor subsequent to radiotherapy. * No chemotherapy or investigational agent for at least 3 weeks prior to the start of SL-701. * Human leukocyte antigen (HLA)-A2 positive. * A tumor tissue sample is provided for immunohistochemical analysis of relevant antigens, immune markers and potential prognostic factors. Preferably a paraffin block or 10-12 unstained slides will be submitted prior to study entry. Participants for whom tumor samples are unavailable or inadequate are permitted to participate in the study; however, the absence of available/adequate tumor specimen must be documented. * Karnofsky performance status (KPS) score ≥ 70%. * Adequate organ function, including the following: * Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL. * Serum creatinine \< 1.5 × the upper limit of normal (ULN). * Bilirubin \< 1.5 × ULN. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 × ULN. * Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the start of SL-701 treatment. * Female participants of childbearing potential and sexually active male participants must agree to use an acceptable form of contraception for heterosexual activity (that is, oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy of their sexual partner(s) for \> 40 days before Screening, during the study, and for 60 days after the last dose of study drug. Men should not donate semen during the study and for 60 days after the last dose of study drug. * Female participants without childbearing potential (spontaneous amenorrhea for \> 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy \> 6 months before Screening) are eligible for inclusion without contraceptive use restriction. * Able and willing to comply with protocol requirements, in the opinion of the investigator. * A written and voluntarily signed informed consent must be obtained from the participant or legally authorized representative, in accordance with local regulations, before the initiation of any study related procedures. The participant or legally authorized representative must be able to read and understand the informed consent form (ICF). Exclusion Criteria: * Prior cancer chemotherapy, bevacizumab (or other vascular endothelial growth factor \[VEGF\]/VEGF receptor \[VEGFR\]-directed agent), or an investigational agent for recurrent/progressive GBM or prior bevacizumab as part of initial therapy (prior chemotherapy or investigational agents are permitted as part of initial therapy; VEGF/VEGFR-directed agents are not permitted). * Contrast-enhancing tumor that is any of the following: * Multi-focal (defined as two separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid-attenuated inversion recovery (FLAIR) or T2 sequences); * Associated with either diffuse subependymal or leptomeningeal dissemination; or * ≥ 4 cm in any dimension. * Requirement of systemic corticosteroid therapy \> 4 mg/day of dexamethasone or equivalent or requirement of increasing dose of systemic corticosteroids during the 7 days prior to the start of SL-701 treatment. * Surgical resection or major surgical procedure within 4 weeks prior to the start of SL-701, or stereotactic biopsy within 7 days prior to the start of SL-701. * Radiation therapy, local therapy (except for surgical re-resection), or systemic therapy following first recurrence/progressive disease. Excluded local therapies include stereotactic radiation boost, implantation of carmustine biodegradable wafers (Gliadel), intratumoral or convection-enhanced delivery administered agents, etc. * Active infection requiring intravenous antibiotics. * History of cancer (other than GBM) within the past 2 years that has metastatic or local recurrence potential and could negatively impact survival and/or potentially confound tumor response assessments within this study. * Clinically significant cardiovascular disease (for example, uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction or stroke within 6 months of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication). * Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus infection, Hepatitis B, or Hepatitis C, or has taken an immunosuppressive agent within 4 weeks prior to the start of SL-701 treatment. Participants with vitiligo, type 1 diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Any condition which in the investigator's opinion makes the participant unsuitable for study participation. * Requires therapeutic anticoagulation with warfarin at baseline; participants must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed. * Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug. * Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are ≤Grade 1 and either post-operative or stable on at least 2 consecutive MRI scans * Has gastrointestinal bleeding or any other hemorrhage/bleeding event National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) \>Grade 3 within 6 months of start of study drug.