Glioblastoma (GBM) is the most common and aggressive type of primary brain tumor, with a high mortality rate. The current standard of care (SoC) in newly diagnosed GBM includes the combination of the alkylating agent Temozolomide (TMZ) with Radiotherapy (RT). The hypothesis of this study is to improve the outcome for patients by combining the current standard of care with the radioligand therapy [177Lu]Lu-NeoB. Patients enrolled into this trial will be treated for up to 32 weeks with the standard regimen TMZ and RT, combined with [177Lu]Lu-NeoB every 4 weeks. In exceptional cases, where patients tolerate and benefit from [177Lu]Lu-NeoB, they can receive up to 10 dose administrations, resulting in a treatment duration of up to 37 weeks. During this period, regular safety and efficacy assessments are planned on a weekly basis. The primary objective of this trial is to estimate the recommended dose of [177Lu]Lu-NeoB in combination with TMZ and RT in participants with newly diagnosed GBM and to characterize the safety and tolerability of this treatment. For this reason, patients will be enrolled and treated in cohorts with increasing dose levels and the totality of available data will be used to define the recommended dose. In an expansion cohort, additional patients will be treated to further characterize the safety and tolerability, as well as to collect preliminary efficacy data from this cohort. Contrast enhanced MRI assessments are recommended to be repeated every 8 weeks and patient reported outcomes (PRO) questionnaires will be used to assess the effect of the study treatment on patient reported symptoms and tolerability. Following treatment, all patients will be followed for up to 5 additional years for safety, progression of disease and survival.~In this study, the term investigational drug refers to [68Ga]Ga-NeoB as radioligand imaging compound, used to explore GRPR expression and to [177Lu]Lu-NeoB, used as radioligand therapy. The term study treatment refers to the combination of [177Lu]Lu-NeoB, temozolomide (TMZ) and radiotherapy (RT).
This study will investigate different doses of [177Lu]Lu-NeoB in combination with RT and TMZ in participants with newly diagnosed GBM with methylated or unmethylated promoter to assess the safety and efficacy of [177Lu]Lu-NeoB in combination with the SoC to identify the recommended dose and to also explore the safety of the PET imaging agent [68Ga]Ga-NeoB and characterize its uptake in the tumor area.