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 Chamberlain; Santosh Kesari; Manmeet Ahluwalia; Debora Ghosh; Adam M Sonabend; Priya Kumthekar

doi:10.1093/noajnl/vdae186

Phase II trial of blood-brain barrier permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma

Neurooncol Adv. 2024 Dec 14;6(1):vdae186. doi: 10.1093/noajnl/vdae186. eCollection 2024 Jan-Dec.

Authors

Crismita Dmello^{1

2}, Andrew Brenner³, David Piccioni⁴, Patrick Y Wen⁵, Jan Drappatz⁶, Maciej Mrugala⁷, Lionel D Lewis⁸, David Schiff⁹, Camilo E Fadul¹⁰, Marc Chamberlain¹¹, Santosh Kesari¹², Manmeet Ahluwalia¹³, Debora Ghosh¹⁴, Adam M Sonabend^{1

2}, Priya Kumthekar^{15

1}

Affiliations

¹ Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois, USA.
² Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
³ Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, Texas, USA.
⁴ Department of Neurosciences, UC San Diego Moores Cancer Center, La Jolla, California, USA.
⁵ Center For Neuro-Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
⁶ Department of Neurology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.
⁷ Fred Hutchinson Cancer Center, University of Washington Medical Center Seattle, Washington, USA.
⁸ Department of Medicine, Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire, USA.
⁹ Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, Virginia, USA.
¹⁰ Division of Neuro-Oncology, Department of Neurology, University of Virginia, Charlottesville, Virginia, USA.
¹¹ Lantern Pharma, Dallas, Texas, USA.
¹² Department of Translational Neurosciences, Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USA.
¹³ Department of Medical Oncology, Miami Cancer Institute, Miami, Florida, USA.
¹⁴ Department of Ophthalmology, Boston Children's Hospital, Harvard Medical Center, Boston, Massachusetts, USA.
¹⁵ Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.

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.

Keywords: ANG1005; high-grade glioma; paclitaxel; phase II clinical trial.

Associated data

ClinicalTrials.gov/NCT01967810