Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma

Axel H Schönthal; David M Peereboom; Naveed Wagle; Rose Lai; Anna J Mathew; Kyle M Hurth; Vincent F Simmon; Steven P Howard; Lynne P Taylor; Frances Chow; Clovis O da Fonseca; Thomas C Chen

doi:10.1093/noajnl/vdab005

Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma

Neurooncol Adv. 2021 Feb 12;3(1):vdab005. doi: 10.1093/noajnl/vdab005. eCollection 2021 Jan-Dec.

Authors

Axel H Schönthal¹, David M Peereboom², Naveed Wagle³, Rose Lai⁴, Anna J Mathew⁵, Kyle M Hurth⁵, Vincent F Simmon⁶, Steven P Howard⁷, Lynne P Taylor⁸, Frances Chow⁴, Clovis O da Fonseca^{6

9}, Thomas C Chen^{5

6

10}

Affiliations

¹ Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
² Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA.
³ Department of Oncology, Providence St. Johns Medical Center, Santa Monica, California, USA.
⁴ Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
⁵ Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
⁶ NeOnc Technologies, Inc., Los Angeles, California, USA.
⁷ Department of Radiation Oncology, University of Wisconsin, Madison, Wisconsin, USA.
⁸ Department of Medicine, University of Washington, Seattle, Washington, USA.
⁹ Department of General and Specialized Surgery, Antonio Pedro University Hospital, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
¹⁰ Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Abstract

Background: Better treatments for glioblastoma (GBM) patients, in particular in the recurrent setting, are urgently needed. Clinical trials performed in Brazil indicated that intranasal delivery of perillyl alcohol (POH) might be effective in this patient group. NEO100, a highly purified version of POH, was current good manufacturing practice (cGMP) manufactured to evaluate the safety and efficacy of this novel approach in a Phase I/IIa clinical trial in the United States.

Methods: A total of 12 patients with recurrent GBM were enrolled into Phase I of this trial. NEO100 was administered by intranasal delivery using a nebulizer and nasal mask. Dosing was 4 times a day, every day. Four cohorts of 3 patients received the following dosages: 96 mg/dose (384 mg/day), 144 mg/dose (576 mg/day), 192 mg/dose (768 mg/day), and 288 mg/dose (1152 mg/day). Completion of 28 days of treatment was recorded as 1 cycle. Adverse events were documented, and radiographic response via Response Assessment in Neuro-Oncology (RANO) criteria was evaluated every 2 months. Progression-free and overall survival were determined after 6 and 12 months, respectively (progression-free survival-6 [PFS-6], overall survival-12 [OS-12]).

Results: Intranasal NEO100 was well tolerated at all dose levels and no severe adverse events were reported. PFS-6 was 33%, OS-12 was 55%, and median OS was 15 months. Four patients (33%), all of them with isocitrate dehydrogenase 1 (IDH1)-mutant tumors, survived >24 months.

Conclusion: Intranasal glioma therapy with NEO100 was well tolerated. It correlated with improved survival when compared to historical controls, pointing to the possibility that this novel intranasal approach could become useful for the treatment of recurrent GBM.

Keywords: O6-methylguanine-DNA methyltransferase; intranasal; isocitrate dehydrogenase 1; perillyl alcohol; recurrent glioblastoma.