Dose Finding Study of [177Lu]Lu-NeoB in Newly Diagnosed Glioblastoma and in Recurrent Glioblastoma

Newly diagnosed glioblastoma: Glioblastoma 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 glioblastoma includes the combination of the alkylating agent Temozolomide (TMZ) with Radiotherapy (RT). The hypothesis of this study is to improve the outcome for participants by combining the current standard of care with the radioligand therapy \[177Lu\]Lu-NeoB. Participants with newly diagnosed glioblastoma enrolled into this trial will be treated with the standard regimen TMZ and RT, combined with \[177Lu\]Lu-NeoB every 4 weeks (Q4W) for 6 administrations. In cases where participants tolerate and benefit from \[177Lu\]Lu-NeoB, they can receive an additional 4 doses (total up to 10 dose administrations). During this period, regular safety and efficacy assessments are planned on a weekly basis. The primary objective of this trial is to identify the recommended dose of \[177Lu\]Lu-NeoB in combination with TMZ and RT in participants with newly diagnosed glioblastoma and to characterize the safety and tolerability of this treatment. For this reason, participants 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. Contrast enhanced MRI assessments are to be repeated every 8 weeks. Participants with newly diagnosed glioblastoma will undergo a baseline \[68Ga\]Ga-NeoB PET/CT or PET/MRI after the surgery/biopsy of the tumor. Recurrent glioblastoma: Participants with recurrent glioblastoma (GBM) carry a dismal prognosis and a short survival. Median overall survival (OS) is approximately 12 months on a population level, 15-18 months in clinical trial populations, and 5-year survival is less than 10%. GBM is one of the lowest long-term survival rates of malignant brain tumors with a 5-year overall relative survival of only 6.8%. The primary objective in recurrent glioblastoma is to determine the recommended dose of \[177Lu\]Lu-NeoB as single agent and to characterize the safety and tolerability of this treatment. For this reason, participants 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 this study, all participants with recurrent glioblastoma will undergo \[68Ga\]Ga-NeoB PET scan to assess GRPR expression during the screening period. Treatment Duration: \[177Lu\]Lu-NeoB will be given every 4 weeks for up to 6 administrations in newly diagnosed glioblastoma (24 weeks in duration) and every 3 weeks for up to 6 administrations (18 weeks in duration) in recurrent glioblastoma. In cases where participants tolerate and benefit from \[177Lu\]Lu-NeoB, they could receive up to 4 additional doses (up to 37 weeks in newly diagnosed glioblastoma and up to 30 weeks in recurrent glioblastoma). Follow-up Duration: During the follow-up period of 12 months participants will be monitored for safety and efficacy with contrast-enhanced MRI every 8 weeks until confirmed disease progression. Follow-up for survival will be monitored until completion of the follow-up period. A full and final analysis will be performed when all participants across all groups have completed the 12 months follow-up period.