Phase II trial of blood–brain barrier permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma
Crismita Dmello, Andrew Brenner, David Piccioni, Patrick Y Wen, Jan Drappatz, Maciej Mrugala, Lionel D. Lewis, David Schiff, Camilo E. Fadul, Marc C. Chamberlain, Santosh Kesari, Manmeet S. Ahluwalia, Debora Ghosh, Adam M. Sonabend, Priya Kumthekar
Abstract
Abstract Background This study is a phase II clinical trial to evaluate the efficacy, safety, and tolerability of the blood–brain barrier (BBB) permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma (HGG) (NCT01967810). Methods Seventy-three patients were enrolled in 3 separate arms-recurrent glioblastoma (GBM) (Arm 1), bevacizumab refractory GBM (Arm 2), and grade 3 anaplastic gliomas (AGs) (Arm 3). The study was started in October 2013, and the data were locked on September 29, 2017. Safety was evaluated for all three arms (n = 73), and the primary endpoint for Arms 1 and 3 was objective response rate (ORR), and Arm 2 primary endpoint was progression-free survival rate at 3 months (PFS3). Results Overall, the safety of ANG1005 was found to be consistent with a taxane toxicity profile. Otherwise, the primary efficacy endpoints of ORR and PFS were not met. The most common adverse events (AEs) were hematologic (32.9%), alopecia (31.5%), and fatigue (30.1%). The median PFS was 1.4 months (95% CI: 1.4, 2.1) and similar across all the treatment arms. The median overall survival was 13.4 months (95% CI: 3.4, 14.6) in Arm 1, 5.8 months (95% CI: 1.9, 9.7) in Arm 2, and 18.2 months (95% CI: 10.7, 35.3) in Arm 3. Conclusion A dose of 600 mg/m2 was determined to be safe in this study. However, the primary efficacy endpoint was not met in the NCT01967810-ANG1005 trial, and no further studies are planned in the glioma setting with this compound.