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 \< 150 kg.
* Karnofsky performance score \> 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