FDA Gives RPDD to NEO100 for Pediatric-Type Diffuse High-Grade Glioma

US FDA

The FDA has granted rare pediatric disease designation (RPDD) to perillyl alcohol (NEO100) for the treatment of patients with pediatric-type diffuse high-grade gliomas (HGG).1

A phase 1b dose-finding trial (NCT06357377), which has yet to begin recruiting patients, will assess NEO100’s safety, brain tumor delivery, and pharmacokinetics in patients with pediatric-type diffuse HGG.2

“This designation marks a significant milestone in our efforts to develop innovative therapies for children [experiencing] this aggressive form of brain cancer,” Amir Heshmatpour, executive chairman of NeOnc Technologies, stated in a news release.1 “We remain committed to advancing NEO100 through clinical development to bring new hope to patients and families facing this devastating disease.”

The open-label study will include patients ages 5 to 18 years with radiographically confirmed, newly diagnosed or recurrent pediatric-type HGG, including H3 K27–altered diffuse midline glioma (DMG); H3 G34–mutant diffuse hemispheric glioma; grade 3 and 4 H3 wild-type and IDH wild-type diffuse pediatric-type HGG with imaging and/or pathology results that are consistent with DMG; or recurrent malignant tumors that involve the brainstem or posterior fossa.2 Eligible patients also must have recovered from all acute adverse effects (AEs) of prior therapy if they have recurrent or progressive disease. Patients previously treated with the maximum standard pediatric dose of temozolomide (Temodar)—90 mg/m2 per dose continuously during radiation therapy for 42 days—or dexamethasone are allowed on the study. Patients treated with dexamethasone must be receiving a stable or increasing dose of the agent for at least 3 days prior to baseline MRI scan.

Patients will be excluded from the trial if they have a diagnosis of any pediatric-type glioma not described in the inclusion criteria, are currently receiving another investigational drug or other anticancer treatments, or have a known disorder affecting their immune system.

“Receiving the RPDD for NEO100 is a crucial step forward in our mission to develop effective treatments for children facing diffuse high-grade gliomas,” Thomas Chen, MD, PhD, FAANs, chief executive officer and chief science officer of NeOnc Technologies, added in the news release.1 “This designation not only validates the potential of our research, but also strengthens our commitment to delivering innovative therapies that can make a real difference in children’s lives.”

Patients on the study will be treated with intranasal NEO100. The study will follow a dose titration design followed by a standard dose-escalation design to assess safety.2 Of note, brain tumor delivery of NEO100 will be confirmed in each disease subtype through surgical resection and needle biopsy only if clinically indicated and scheduled for clinical purposes. Patients who undergo surgical resection or needle biopsy will be treated with a minimum of 4 days of intranasal NEO100 treatment before the procedure. The study will include 4 cohorts to treat patients on a 28-day cycle with 192 mg of NEO100 4 times a day (cohort 1), 288 mg of NEO100 4 times a day (cohort 2), 384 mg of NEO100 3 times a day (cohort 3), or 576 mg of NEO100 twice a day (cohort 4; ceiling dose).

The primary end point of the study is the nature and severity of AEs; secondary end points include identifying the maximum tolerated dose of NEO100, determining the recommended phase 2 dose, measuring NEO100 and its metabolite perillic acid in brain tumor tissue, blood-brain barrier penetration, characterizing the pharmacokinetics of NEO100, and assessing the efficacy of NEO100 based on objective response rate, progression-free survival, and overall survival.

References

1. NeOnc Technologies Holdings, Inc. receives rare pediatric disease designation for NEO100 in treatment of pediatric-type diffuse high-grade gliomas. News release. NeOnc Technologies. March 31, 2025. Accessed April 3, 2025. https://neonc.com/neonc-technologies-holdings-inc-receives-rare-pediatric-disease-designation-for-neo100/
2. A study of the safety, dosing, and delivery of NEO100 in patients with pediatric brain tumors. ClinicalTrials.gov. Updated October 15, 2024. Accessed April 3, 2025. https://www.clinicaltrials.gov/study/NCT06357377