This is an event driven, adaptive design, a randomized, active-controlled, multicenter,
open-label, parallel groups, Phase 3 study of DSP-7888 Dosing Emulsion plus Bevacizumab
versus Bevacizumab alone in patients with recurrent or progressive glioblastoma multiforme
(GBM) following treatment with first line therapy consisting of surgery and radiation with or
- Patients or their legal representatives must be able to provide written informed
- Histologically confirmed diagnosis of supratentorial GBM (Grade 4 astrocytoma).
- Radiographic evidence of first recurrence or progression of GBM following primary
therapy consisting of surgery (biopsy or resection) and chemoradiation; patients may
have undergone a second debulking surgery following initial recurrence or progression.
Patients whose tumors are O6 methyl guanyl-methyltransferase (MGMT)
methylated-promoter negative need not have received chemotherapy in the past to be
- Human leukocyte antigen type HLA-A*02:01, HLA-A*02:06, or HLA-A*24:02.
- Age ≥18.
- KPS score of ≥60.
- Serum creatinine value <2X the upper limit of normal (ULN) for the reference
- Alanine aminotransferase/aspartate aminotransferase <3X the ULN and total bilirubin
<2× the ULN for the reference laboratory.
- Men and women of childbearing potential must agree to use a reliable method of
contraception (oral contraceptives, implantable hormonal contraceptives, or double
barrier method) or agree to completely refrain from heterosexual intercourse for the
duration of the study and for 180 days following the last dose of DSP-7888 Dosing
- Patients must have recovered from the effect of all prior therapy to Grade 2 or less.
- Patients must be at least 28 days from any major surgery, and any surgery incisions or
wounds must be completely healed.
- Patients must be at least 12 weeks from the completion of prior radiation therapy (RT)
in order to discriminate pseudo progression of disease from progression.
- Patients must be at least 4 weeks from the completion of prior systemic or
- Patients must stop Novo-TTF treatment one day prior to study therapy (no washout
period is needed). However, any wounds from TTF must be adequately healed per
Inclusion Criterion #11.15. For patients who are not receiving therapeutic
anticoagulation treatment, an international normalized ratio (INR) and a PTT ≤ 1.5 ×
the ULN; patients who are receiving anticoagulation treatment should be on a stable
- Patient's left ventricular ejection fraction (LVEF) > 40%. 17. Patient has a resting
pulse oximetry of 90% or higher.
Patients with any of the following will be excluded from the study:
- Prior therapy with Bev.
- Patients with secondary GBM.
- Any anti-neoplastic therapy, including RT, for first relapse or recurrence.
- Evidence of leptomeningeal spread of tumor or any history, presence, or suspicion of
metastatic disease extracranially.
- Evidence of impending herniation on imaging.
- Has known multifocal disease. Multifocal disease is defined as discrete sites of
disease without contiguous T2/FLAIR abnormality that require distinct radiotherapy
ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR
abnormality as the main lesion(s) and that are encompassed within the same
radiotherapy port as the main lesion(s) are permitted.
- Patients with infections that have required treatment with systemic antibiotics within
7 days of first dose of protocol therapy.
- The need for systemic glucocorticoids in doses in excess of 4 mg/day of dexamethasone
or in comparable doses with other glucocorticoids.
- Treatment with any investigational agents within 5 half-lives of the agent in question
or, if the half-life is unknown, within 28 days of enrollment.
- Pregnant or lactating females.
- Prior history of malignancy within 3 years of enrollment other than basal or squamous
cell carcinoma of the skin, cervical intra-epithelial neoplasia, in situ carcinoma of
the breast, or prostate cancer treated with surgery or RT with a prostate specific
antigen of <0.01 ng/mL.
- Patients with active autoimmune diseases within 2 years of enrollment into the study
including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus,
systemic sclerosis, Sjogren's syndrome, Wegener's granulomatosis, ulcerative colitis,
Crohn's disease, myasthenia gravis, Graves' disease, or uveitis except for psoriasis
not requiring systemic therapy, vitiligo or alopecia areata, or hypothyroidism; if an
autoimmune condition has been clinically silent for 12 months or greater, the patient
may be eligible for enrollment.
- Patients on immunosuppressive therapies; the use of topical, inhalational,
ophthalmologic or intra articular glucocorticoids, or the use of physiologic
replacement doses of glucocorticoids are permitted.
- Patients with primary immunodeficiency diseases.
- Patients with significant bleeding in the preceding 6 months or with known
- History of abdominal fistula, intestinal perforation, or intra-abdominal abscess in
the preceding 12 months.
- Positive serology for human immunodeficiency virus (HIV) infection, active hepatitis
B*, or untreated hepatitis C; patients who have completed a course of anti-viral
treatment for hepatitis C are eligible.
o *In cases of negative results for HepB surface antigen with positive HepB core
antibody, HBV DNA testing is required.
- Patient has a medical history of frequent ventricular ectopy, e.g., non-sustained
ventricular tachycardia (VT).
- Significant cardiovascular disease, including New York Hospital Association Class III
or IV congestive heart failure, myocardial infarction within 6 months of enrollment,
unstable angina, poorly controlled cardiac arrhythmias, or stroke within the preceding
- Any other uncontrolled inter current medical condition, including systemic fungal,
bacterial, or viral infection; uncontrolled hypertension; diabetes mellitus; or
chronic obstructive pulmonary disease requiring 2 or more hospitalizations in the
preceding 12 months.
- Any psychiatric condition, substance abuse disorder, or social situation that would
interfere with a patient's cooperation with the requirements of the study.
- Known sensitivity to Bev or any of the components of DSP-7888 Dosing Emulsion.
- Patient has a QTcF (QT corrected based on Fridericia's equation) interval > 480 msec
(CTCAE = Grade 2) or other factors that increase the risk of QT prolongation or
arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT
interval syndrome) at screening. (Patients with bundle branch block and a prolonged
QTc interval should be reviewed by the Medical Monitor for potential inclusion.)
- Patient has dyspnea at rest (CTCAE ≥ Grade 3) or has required supplemental oxygen
within 2 weeks of study enrollment.