Actr-95. Hypoxia Activated Evophosphamide (th-302) for Recurrent Gbm Following Bevacizumab Failure, a Multicenter Phase Ii Study
Year: 2017
Type: conference-abstract
Abstract: TH-302 (evophosphamide) is a hypoxia-activated prodrug that, when activated in hypoxic conditions (<0.5% O2), releases the bis-alkylating agent bromo-isophosphoramide mustard (Br-IPM), which can then act as a DNA crosslinking agent. In vivo, TH-302 has shown to potentiate the anti-tumor efficacy of other antiangiogenic agents. Pur prior phase 1 study with dose expansion showed preliminary activity with a 24% objective response rate and a 26% PFS rate at 4 months. A multicenter, single-arm, two-stage prospective study, non-blinded with combination therapy with bevacizumab at 10 mg/kg intravenously (IV) every 2 weeks and TH-302 at 670 mg/m2 IV every 2 weeks, in 6 week cycles, until disease progression. The primary endpoint is progression free survival at 4 months. Patients underwent baseline assessment for hypoxic burden by 18F-misonidazole PET, dynamic susceptibility contrast (DSC) perfusion imaging, and serum sampling for biomarker analysis. Accrual is complete with 36 patients receving study drug. Treatment was well tolerated, with adverse events as expected and the most common toxicity rash along the perineum. While 6 patients remain on treatment, 6 of the required 7 PFS4 events have occured with one more needed to meet the designated positive endpoint. Correlation with imaging and serum biomarkers is ongoing and may help further define the subset of patients with the greatest benefit. Evofosfamide appears to have clinically meaningful activity in bevacizumab refractory glioblatoma. Results will be updated.
Source: Neuro-Oncology
Authors: Andrew Brenner, David Reardon, Patrick Wen, Peter Fox, Shiliang Huang, Mark Muzi, Yichu Liu, Eudocia Lee
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767628544