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 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 initiat