NeOnc Reports 48.9% Six-Month PFS With NEO100 in IDH1-Mutant Glioma

NeOnc Technologies reported positive topline results from the Phase 2a portion of the NEO100-01 study (NCT02704858), an open-label, multicenter Phase 1/2a trial evaluating intranasal NEO100 in patients with recurrent or progressive Grade III and Grade IV IDH1-mutant glioma.

The study met its primary endpoint, with six-month progression-free survival (PFS-6) of 48.9% (95% CI, 26.3%-68.1%) by RANO 2.0 criteria using Kaplan-Meier estimation. This compared with a 20% prespecified benchmark for standard of care (p=0.0047).

The Phase 2a portion enrolled 24 of a planned 28 patients at the recommended Phase 2 dose of 1,152 mg/day. NEO100 was self-administered intranasally four times daily in 28-day cycles until progression, death or withdrawal. MRI scans were assessed by an independent central reviewer, and efficacy results were reported for the intent-to-treat population.

Survival and Disease Control

Median overall survival (OS) was 26.09 months, with 12 deaths among the 24 patients. Estimated OS was 86.7% at six months, 60.9% at 12 months and 54.1% at 24 months.

Five patients remained on treatment at the time of the analysis. One remained progression-free for approximately 19 months, while another achieved a partial response sustained for 114 days through Cycle 8 and remained on treatment. The objective response rate was 8.3%, with two of 24 patients achieving an objective response by RANO 2.0.

The survival findings compare favourably with historical outcomes reported in recurrent brain-tumor settings, where median OS in several second-line studies has ranged from approximately 5.6 to 9.1 months. These historical comparisons are not randomized comparisons with NEO100 but provide context for the reported 26.09-month median OS.

NEO100 Addresses an Unmet Need

NEO100-01 enrolled patients with Grade III and Grade IV IDH1-mutant glioma that had recurred or progressed following radiation or combined temozolomide and radiation. According to NeOnc, no approved targeted therapy is currently available for this recurrent high-grade population.

NEO100 is an ultra-pure pharmaceutical-grade formulation of perillyl alcohol administered intranasally at home. The delivery approach is designed to reach the brain through the olfactory and trigeminal pathways. Perillyl alcohol has demonstrated pleiotropic anticancer effects in preclinical studies, including cell-cycle arrest, endoplasmic-reticulum stress and activation of apoptotic pathways, although its precise anticancer mechanism remains incompletely established.

Favorable Tolerability Profile

No major toxicities were reported across the Phase 2a cohort, and adverse events were predominantly low-grade. The company said the findings were consistent with the Phase 1 experience, in which NEO100 was well tolerated without severe or dose-limiting toxicities.

Several patients have remained on daily intranasal treatment for more than one year. Detailed safety findings from the full Phase 2a dataset are expected to be presented at a future medical meeting.

FDA Type B Meeting Planned

NeOnc intends to request a Type B meeting with the U.S. Food and Drug Administration to align on a registrational development path for NEO100 in recurrent IDH1-mutant high-grade glioma.

Additional prespecified analyses, including Grade III versus Grade IV subgroup results, pharmacokinetics and quality-of-life measures, remain ongoing. The company plans to report these analyses separately and present the full Phase 2a dataset, including detailed safety findings, at a future medical meeting.

The Phase 2a findings should be interpreted in the context of the study’s small, open-label, single-arm design and absence of a concurrent randomized control group. The PFS-6 result was compared with a prespecified benchmark rather than a randomized comparator. The planned FDA meeting will help define the appropriate registrational development strategy for NEO100.

Reference

NeOnc Technologies Reports Positive Topline Phase 2a Results for Intranasal NEO100 in Recurrent IDH1-Mutant High-Grade Glioma – NeOnc Technologies Holdings, Inc.