In an expanded 25-patient Phase 1/2a plus compassionate-use cohort of recurrent WHO Grade III/IV IDH1-mutant astrocytoma, intranasal NEO100 produced a 24% radiographic remission rate (6/25), six-month progression-free survival of 44%, and 36% of patients alive at or beyond 18 months from treatment start. No significant toxicity has been reported with prolonged chronic dosing, per the sponsor. The remission and PFS-6 figures exceed commonly cited historical benchmarks for salvage therapy in this setting (<8% response; 21–31% PFS-6). The core update is incremental but directionally consistent: NeOnc Technologies has added one additional patient achieving both radiographic remission and long-term survival since a November data point, bringing the evaluable aggregate to 25 and reinforcing a signal previously observed across Phase 1, Phase 2a, and one compassionate-use case. All assessments used RANO criteria. The company frames the results as evidence that an intranasal, CNS-penetrant metabolic therapy can drive radiographic remissions in a population where response has been rare. Strategically, NeOnc is leaning into two differentiators: route of administration and biology. Intranasal delivery as a blood–brain barrier workaround is the operational thesis, potentially enabling higher CNS exposure without systemic toxicity seen with cytotoxic or anti-angiogenic salvage regimens. Targeting IDH1-mutant high-grade glioma narrows the addressable population but ties the program to a molecularly defined group with distinct natural history and growing regulatory interest following approvals in earlier-grade IDH-mutant disease. The trade-off is evidentiary: the current dataset is single-arm, small, and includes a compassionate-use case, with outcomes benchmarked to historical controls. That will not carry a registration conversation in high-grade glioma without a randomized comparator and blinded imaging review. For sites and CROs, the operational profile is attractive. An at-home intranasal regimen with low reported toxicity could reduce chair time and supportive care burden, shift visits toward imaging and safety labs, and open participation to community neuro-oncology centers that struggle with intensive infusion protocols. Adherence verification, training on device use, and reliable home supply logistics will become central operational variables. Imaging vendors and independent review committees will be pivotal, as regulatory credibility will hinge on blinded central reads, control of steroid confounding, and rigorous application of RANO in an IDH-mutant, post-treatment landscape where pseudoresponse and treatment effects can cloud interpretation. Sponsors should view the bar for the next study as clear but high. A randomized Phase 2/3 trial against lomustine, bevacizumab-based salvage, or other relevant standards is likely necessary, with PFS and OS as co-primary or hierarchical endpoints and pre-specified analyses by MGMT status, prior bevacizumab exposure, extent of resection, and steroid use at baseline. Given the outpatient modality, a hybrid or decentralized visit schedule with centralized imaging could accelerate enrollment and broaden access, but will require robust ePRO/adherence capture and remote safety monitoring. Manufacturing scale-up for a chronic intranasal formulation, device labeling considerations, and chain-of-custody controls for home dispensing will also need early attention. Near term, watch for the complete Phase 2a readout, including duration of response, time on corticosteroids, dose-intensity/adherence data, and any signal on health-related quality of life. Clarity on the pivotal design, comparator selection, and plans for blinded independent central review will indicate whether NeOnc is positioning for an accelerated path in a niche subset or building toward a conventional registrational package. The central risk remains external validity: can a small, historically benchmarked signal translate under randomization and independent imaging scrutiny in a heterogeneous, heavily pretreated high-grade glioma population?
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
