Intranasal NEO100 Meets Primary End Point in Recurrent IDH1-Mutant Glioma

Positive topline results from the phase 2a portion of NEO100-01 (NCT02704858), a study of intranasal NEO100 (purified perillyl alcohol) in patients with recurrent or progressive grade III and grade IV IDH1-mutant glioma, show that the study met its primary end point, with a 6-month progression-free survival (PFS-6) rate of 48.9% (95% CI, 26.3%-68.1%) by RANO 2.0 criteria and Kaplan-Meier estimation, compared with a prespecified 20% benchmark for standard of care (P =.0047).¹

Secondary survival findings were supportive. Median overall survival (OS) was 26.09 months among the 24 treated patients, with 12 deaths recorded. OS rates were 86.7% (95% CI, 64.3%-95.5%) at 6 months, 60.9% (95% CI, 36.4%-78.4%) at 12 months, and 54.1% (95% CI, 29.5%-73.4%) at 24 months. Objective response rate was 8.3% (n = 2/24 patients) by RANO 2.0 criteria. Five patients remain on active treatment, including 1 who has been progression-free for approximately 19 months and a second whose partial response has been sustained through the end of cycle 8, or 114 days.

Based on these findings, NeOnc, the sponsor, intends to request a type B meeting with the FDA to align on a registrational development path for NEO100 in recurrent IDH1-mutant high-grade glioma, a setting with no approved targeted therapy.

Study Design

NEO100-01 is an open-label, multicenter phase 1/2a study of intranasal NEO100 in patients with radiographically confirmed recurrence or progression of primary or secondary grade IV glioma, or grade III astrocytoma, harboring an IDH1 mutation.² All enrolled patients had previously failed radiation therapy or combined temozolomide (Temodar) and radiation. The phase 2a portion enrolled 24 of a planned 28 patients at the recommended phase 2 dose of 1152 mg/day, self-administered intranasally 4 times daily in 28-day cycles until progression, death, or withdrawal.¹

The primary end point was the PFS rate at 6 months. Secondary end points included objective response rate by RANO 2.0 criteria, PFS, OS, safety and tolerability, pharmacokinetics, and quality of life. All MRI scans were reviewed by an independent central reviewer, and efficacy results are reported for the intent-to-treat population.

"We set out to reach the brain directly, delivering therapy through the nose and along the olfactory pathway rather than forcing a drug past the blood-brain barrier, and what we are seeing in phase 2a is what our biology predicted,” said Thomas C. Chen, MD, PhD, founder, chief medical officer and chief scientific officer of NeOnc, in a news release.

Safety and Tolerability

NEO100 was well tolerated across the cohort, with no major toxicities reported to date and adverse events described as predominantly low-grade.¹ That profile is consistent with the phase 1 portion of the study, in which no severe or dose-limiting toxicities were observed at any dose level. Several patients have remained on daily intranasal dosing for more than a year without significant toxicity, which the company said reflects a delivery route designed to reach the brain while avoiding systemic cytotoxic exposure.

Clinical Context and Limitations

Approximately 90% of patients with high-grade glioma recur within 6 to 9 months of maximal therapy, and repeat surgery is often not feasible at recurrence.¹

NEO100-01 was a single-arm, open-label study of 24 patients that did not reach its planned enrollment of 28 and was not powered as a confirmatory trial. No randomized control arm was used, and comparisons with historical data are limited by differences in patient population, era, and assessment criteria. Additional prespecified analyses, including a grade III vs grade IV subgroup analysis, pharmacokinetics, and quality-of-life measures, are ongoing and will be reported separately; NeOnc plans to present the full phase 2a data set, including detailed safety findings, at a future medical meeting.

REFERENCES

1. NeOnc Technologies reports positive topline phase 2a results for intranasal NEO100 in recurrent IDH1-mutant high-grade glioma. News release. NeOnc Technologies Holdings, Inc. August 12, 2026. Accessed August 14, 2026. https://tinyurl.com/2yhey89v

2. Safety and efficacy study in recurrent or progressive grade III or IV IDH1 mutated glioma. ClinicalTrials.gov. Updated December 9, 2024. Accessed August 14, 2026. https://clinicaltrials.gov/study/NCT02704858