Early safety data from the phase 2b RESTORE study, evaluating NanO2 in combination with radiation and temozolomide for newly diagnosed glioblastoma, were presented at the 2024 Society for Neuro-Oncology Annual Meeting. The study aims to improve treatment outcomes by enhancing oxygen delivery to hypoxic tumor regions.
Addressing Hypoxia in Glioblastoma Treatment
Glioblastoma is characterized by extensive hypoxic regions, which can lead to treatment resistance. Radiation-induced cell death relies on oxygen, and hypoxic conditions allow cancer cells to repair DNA strand breaks. Similarly, chemotherapy efficacy is reduced in hypoxic cells due to limited drug diffusion and delivery. The RESTORE trial hypothesizes that NanO2 can boost oxygen delivery, thereby enhancing the effectiveness of chemoradiation.
RESTORE Trial Design and Patient Population
The RESTORE trial is a double-blind, prospective, placebo-controlled study. It enrolled patients aged 18 years or older with histologically confirmed, newly diagnosed primary or secondary glioblastoma multiforme. Key inclusion criteria included a Karnofsky performance status of at least 70 and a life expectancy of at least 3 months. Patients with recurrent glioblastoma who had received prior therapy (excluding surgical resection) were excluded.
Patients received standard chemoradiation consisting of 30 fractions of focal radiation (60 Gy in 2 Gy fractions, 5 days per week for 6 weeks) with concurrent temozolomide (75 mg/m2 for 6 weeks). Participants were randomized 1:2 to receive either placebo or NanO2 infusion immediately before each radiation dose, while continuously breathing oxygen. After chemoradiation, treatment was paused for 4 weeks before adjuvant temozolomide.
Safety Profile and Patient Characteristics
As of the August 2024 data cutoff, 22 patients were enrolled. The most common non-serious adverse events (AEs) were related to the nervous system, general disorders, gastrointestinal issues, respiratory and thoracic problems, skin and subcutaneous issues, infections, injuries, investigations, musculoskeletal issues, vascular problems, psychiatric issues, metabolic issues, eye and ear/labyrinth issues, renal and urinary issues, blood and lymphatic issues, and endocrine issues. 63.6% of patients had MGMT unmethylated tumors, and 36.4% had methylated tumors. The mean patient age was 62.9 years (range, 39-77), with a majority being White (95.5%).
Adverse Events and Causality
Per site assessment, most serious treatment-emergent AEs (TEAEs) were deemed unrelated to the study medication. A few were considered unlikely or possibly related. Medical monitors largely concurred, with most serious TEAEs considered unrelated to NanO2. Some serious TEAEs were possibly or probably related to radiation, while others had a causal relationship with disease progression. Only one serious TEAE was considered causally related to temozolomide.
The trial is ongoing, with an estimated completion date of September 2025.
