Intranasal Treatment Meets Primary End Point in IDH1-Mutated Glioma

The phase 2a portion of the NEO100-01 trial assessing intranasal NEO100 in patients with recurrent or progressive grade III and IV IDH1-mutant glioma met its primary end point of 6-months progression-free survival (PFS-6), according to a press release from NeOnc, the drug’s developer.¹

By RANO 2.0 criteria using Kaplan-Meier estimation, the PFS-6 was 48.9% (95% CI, 26.3%-68.1%). Of note, the rate prespecified in the study design as the expectation for the standard of care was 20% (P = .0047).

The median overall survival (OS), a secondary end point, was 26.09 months. Among 24 patients, 12 had died. At 6 months, the OS rate was 86.7% (95% CI, 64.3%-95.5%), 60.9% (95% CI, 36.4%-78.4%) at 12 months, and 54.1% (95% CI, 29.5%-73.4%) at 24 months.

The objective response rate was 8.3% by RANO 2.0 criteria. Across the cohort, 5 of 24 patients remained on treatment, with 1 patient remaining progression-free for approximately 19 months. Additionally, a second patient had a partial response for 114 days through the end of cycle 8 and remains on treatment with a response.

No major toxicities have been reported, and most have been low-grade. These results are consistent with the phase 1 portion of the trial, and no severe or dose-limiting toxicities have occurred.

“In recurrent high-grade glioma, the outcome that matters is how long a patient can hold the disease at bay and still live their life,” said Josh Neman, PhD, chief clinical officer of NeOnc in the press release.¹ “Five of our 24 patients remain on therapy, one progression-free approaching 19 months and another in an ongoing response approaching 4 months, and they are taking this treatment at home rather than in an infusion chair. Durability and tolerability together are rare at recurrence, and we believe that combination is what these data point to. We look forward to discussing the findings with the FDA.”

The NEO100-01 trial enrolled patients with grade III/IV IDH1-mutant tumors, which have progressed after radiation and treatment with temozolomide (Temodar). NEO100 is administered intranasally 4 times a day for 28-day cycles by the patient at home.

To be included in the trial, patients must have radiographically confirmed progression of or recurrent primary or secondary grade IV glioma; radiographically confirmed progression of, recurrent, primary, or secondary grade III astrocytoma; be on stable or decreasing dose of steroids for at least 5 days prior to the date of informed consent; prior radiation treatment or radiation plus temozolomide must have failed the patient.²

Specifically, to be eligible for the phase 2a portion, patients must have confirmed IDH1 mutation by reverse transcription polymerase chain reaction or immunohistochemistry. However, if patients were continuing into phase 2a from the phase 1 portion of the study, this was not needed.

Patients were excluded from treatment if they had a tumor greater than 30 mm as assessed in a baseline MRI; a multi-focal tumor; the patient has received chemo-radiation within 90 days of the first administration of NEO100; surgery occurred within 7 days prior to the date of informed consent; or the patient had received any form of anti-cancer therapy within 28 days prior to first administration of the study drug.

The company is planning to request a Type B meeting with the FDA regarding the registrational development path for NEO100 in this patient population. Additional analyses are ongoing and include the grade III vs grade IV subgroup analysis, pharmacokinetics, and quality of life. The full phase 2a data are expected to be presented at an upcoming medical meeting.

“These results represent an important milestone for NeOnc and, more importantly, a source of hope for patients with recurrent high-grade glioma who currently have very limited treatment options. NEO100 met the study’s primary end point, demonstrated encouraging survival outcomes, and was administered intranasally by patients at home with no major toxicities reported. We believe these findings support the potential of our intranasal delivery platform to address one of the greatest challenges in treating brain cancer - the blood-brain barrier. Our priority now is to engage with the FDA and align on the most efficient path toward a registrational study,” said Amir F. Heshmatpour, executive chairman, president and chief executive officer of NeOnc, in the release.¹

References

1. NeOnc Technologies reports positive topline phase 2a results for intranasal NEO100 in recurrent IDH1-mutant high-grade glioma. News release. August 12, 2026. Accessed August 13, 2026. https://tinyurl.com/2ssa4be7
2. Safety and efficacy study in recurrent or progressive grade III or IV IDH1 mutated glioma. ClinicalTrials.gov. Updated July 16, 2026. Accessed August 13, 2026. https://tinyurl.com/ysttemf7