On September 12, 2024 NH TherAguix (NHT), a phase II clinical-stage biotechnology company specializing in the development of novel nanomedicine solutions for precision radiotherapy in oncology, reported the completion of enrollment in NANO-GBM phase Ib/II trial, evaluating the combination of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed glioblastoma and the publication of the positive Phase Ib outcomes and MRI-based biodistribution data from this trial in the journal Clinical and Translational Radiation Oncology under the title "NANO-GBM trial of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed Glioblastoma: Phase Ib outcomes and MRI-based biodistribution" (Press release, NH TherAguix, SEP 12, 2024, View Source [SID1234646535]).
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Glioblastoma progression occurs mainly within the tumor volume after treatment by radiotherapy. To address this challenge, a radiosensitization strategy with intravenous administration of AGuIX nanoparticles is being explored in the NANO-GBM phase Ib/II trial (NCT04881032), which is the firstin-human use of these nanoparticles with radiotherapy and chemotherapy for the treatment of newly diagnosed glioblastoma.
Developed by NH TherAguix, AGuIX is designed to improve tumor targeting and increase radiobiological damage to tumor tissue locally, thanks to its radiation signal amplification capabilities, in the purpose of expanding lifespan of cancer patients
Enrollment completion
Nano-GBM is a multicentric, randomized, open-label and non-comparative Phase Ib/II trial. These patients with unresected or partially resected glioblastoma receive four injections of AGuIX in combination with temozolomide (75 mg/m²/day) and radiotherapy (60 Gy in 30 fractions of 2 Gy), followed by adjuvant temozolomide according to Stupp protocol, as the standard of care.
The aim of the phase IIstudy is to randomize patients within two arms: i) an experimental arm in which patients are treated with AGuIX at a dose of 100 mg/kg in combination with radio chemotherapy (40 patients), and ii) a control arm in which patients are treated with radio chemotherapy alone (20 patients). To date, all patients of the phase II have been successfully enrolled.
The primary endpoint of this phase II study is progression-free survival at 6 months. Secondary endpoints include AGuIX distribution in tumors, progression-free survival, overall survival, overall objective response rate and the safety profile of AGuIX in combination with radiotherapy and temozolomide.
The Phase II final data are expected by mid-2026.
In May 2024, AGuIX has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as a next-generation radio-enhancer for the treatment of malignant gliomas, particularly glioblastoma (GBM). The Company has recently submitted a dossier for a PRIME designation from the European Medical Agency (EMA).
NH TherAguix is also preparing to launch a multicentric, randomized, double-blind pivotal trial in patients with recurrent glioblastoma in 2025.
Publication of the positive Phase Ib outcomes and MRI-based biodistribution
In the Phase Ib part of the NANO-GBM trial, eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed glioblastoma with unresected or partially resected glioblastoma. A dose escalation approach was applied to assess 3 dose levels of AGuIX: 50 mg/kg, 75 mg/kg and 100 mg/kg. Patients were treated with radiotherapy (60 Gy), and concomitant and adjuvant temozolomide. Four intravenous injections of AGuIX were delivered during radiotherapy and concomitant temozolomide.
The goal of the phase Ib was to determine the recommended phase II dose (RP2D) by the evaluation of the occurrence of dose-limiting toxicity (DLT), and to evaluate pharmacokinetic and AGuIX biodistribution in glioblastoma on MRI based images.
Eight patients were enrolled and have successfully received four intravenous injections of AGuIX: at 50 mg/kg (1 patient), 75 mg/kg (1 patient), and 100 mg/kg (6 patients). No AGuIX-related DLTs were observed, leading to the determination of the RP2D of AGuIX as 100mg/kg for continuation in the ongoing phase II multicenter randomized trial.
Moreover, the pharmacokinetic data confirmed previous results obtained in the Nanorad study, with AGuIX mean AUC increasing with dose and a mean plasmatic half-life ranging from 0.84 to 1.41 h.
The quantification assessment confirmed the precise and specific biodistribution of AGuIX within the glioblastoma allowing to identify regions with different AGuIX concentration levels, ranging from: moderate (36-123 µM) to high (123-291 µM) and very high (> 291 µM) concentration. These values are in agreement with range of concentration high enough for inducing a radiosensitization effect according to NH TherAguix knowledge and experience.
These results confirm the good safety profile of AGuIX (with no occurrence of severe AGuIX-related toxicity) and the widespread dispersion of nanoparticles throughout glioblastoma. Those outcomes support progression to the multicenter and randomized phase II, utilizing an RP2D of AGuIX of 100mg/kg (4 injections).