BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study
PSMA expression has been demonstrated in the tumor neovasculature of Glioblastoma Multiforme
(GBM) by immunohistochemical staining. Strong reactivity to the antibody component of PSMA
ADC was observed in the endothelial cells of new tumor blood vessels in GBM. Since the
endothelial cells are located on the luminal surface of blood vessels, PSMA ADC does not
need to cross the blood brain barrier to reach its target. Following binding and
internalization of PSMA ADC, the cytotoxic component of PSMA ADC will be released and
destroy the neovasculature that supports tumor growth. Therefore, PSMA ADC may be an active
treatment for GBM.
Bevacizumab, an inhibitor of angiogenesis, has been shown to be effective in improving
progression-free survival as a single agent. Thus PSMA ADC, which targets tumor
angiogenesis by a mechanism different from that of bevacizumab, may be a novel therapeutic
modality for GBM.
A phase 2 study of PSMA ADC is proposed for patients with GBM that have progressed after
standard treatment that includes radiation, temozolomide and bevacizumab. A phase 1 study of
PSMA ADC in prostate cancer is ongoing and a phase 2 dose level of 2.5 mg/kg IV every 3
weeks has been defined. Treatment after bevacizumab failure for patients with GBM is a major
unmet medical need. If activity were demonstrated in this trial, a definitive randomized
study would be proposed.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate for patients with glioblastoma that have progressed after prior treatment that has included radiation, temozolomide and bevacizumab.
3 months until progression, potentially up to 1 year
Rees Cosgrove, MD
United States: Food and Drug Administration
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