BrUOG 263: Prostate Specific Membrane Antigen (PSMA) Glioblastoma Multiforme (GBM)

Inclusion Criteria

• Males and females Histologically confirmed GBM (Patients with gliosarcoma are also eligible)
• Assessable or measurable disease by MRI
• Progression after prior treatment that includes radiation, temozolomide and bevacizumab.

-> 4 weeks since prior chemotherapy, bevacizumab and other systemic treatment and > 3 weeks from prior radiation.

• age >18 years
• Weight 60
• Life expectancy >12 weeks
• Brain MRI within 21 days prior to registration
• Laboratory results requirements
• Absolute neutrophil count (ANC) ≥ 1000/mm3.
• Platelets (Plt) ≥ 100,000/mm3
• Hemoglobin (Hgb) ≥ 8.0 g/dL
• Total bilirubin ≤ 2.0 mg/dL
• Serum alanine transferase/ Serum aspartate transaminase (ALT/AST) ≤ 2.5x the upper limit of normal (ULN)
• Serum creatinine ≤ 2.0 mg/dL
• Pancreatic Amylase (p-amylase) ≤ the ULN
• Negative serum pregnancy test for women of child-bearing potential
• Stable corticosteroid dose at least 14 days prior to registration
• Women of childbearing potential must have a negative pregnancy test.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
• Patients must not be on enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on non-enzyme inducing anti-epileptic drugs (NEIAED) or may not be taking any anti-epileptic drugs. A list of AED that cause modest or no induction of hepatic metabolic enzymes will be discussed

Exclusion Criteria

• Non-GBM primary invasive malignant neoplasm within the five years prior to screening except for:
• keratinocyte (non-melanoma) (i.e., basal cell, squamous cell) carcinoma of the skin; or low-grade papillary superficial transitional cell carcinoma of the bladder.However, patients with stage 1 cancers not requiring cancer therapy including chemotherapy or hormone therapy, for which a lifespan of greater than 3 years without treatment is expected (such as early stage prostate cancer) may be enrolled.
• Clinically significant cardiac disease (New York Heart Association Class III/ IV or severe debilitating pulmonary disease
• Subjects with QTc>500 msec (either Bazzett's or Fridericia's method)
• Radiation therapy, cytotoxic chemotherapy, bevacizumab or other treatment for GBM within previous three weeks
• Evidence of an active infection requiring ongoing intravenous antibiotic therapy
• Any toxicity ≥ grade 2 (non-laboratory) (NCI CTCAE, Version 4.03) prior to first dose of study drug
• Prior treatment with PSMA ADC or other therapies targeting PSMA, or other anti-body drug conjugate (ADC) products that contain monomethyl auristatin E (MMAE) (e.g., brentuximab vedotin, glembatumumab vedotin, ASG-5ME)
• Known hypersensitivity reactions to PSMA ADC or any of its components.
• Any medical condition that in the opinion of the Investigator may interfere with a subject's participation in or compliance with the study
• Patients with a prior history of pancreatitis