Unknown Cancer NIHR-supported project Brain & Nervous System

Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-NeoB in Combination with Radiotherapy and Temozolomide in Subjects with Newly Diagnosed Glioblastoma and as a Single Agent in Recurrent Glioblastoma

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A radioactive drug that seeks out tumour cells is being tested in combination with standard chemotherapy and radiotherapy for people with glioblastoma, the most aggressive form of brain cancer. Glioblastoma kills most patients within a year or two of diagnosis, and treatment has barely changed in decades. The current standard of care—a chemotherapy drug called Temozolomide plus radiotherapy—extends survival by only a few months. This trial tests whether adding a targeted radioligand therapy, [¹⁷⁷Lu]Lu-NeoB, can improve outcomes without unacceptable toxicity. The drug binds to receptors on glioblastoma cells and delivers a localised radiation dose. If the approach proves safe and effective, it could offer a new treatment option for a disease that currently has few. For newly diagnosed patients, the combination might extend survival beyond what standard care alone achieves. For those whose tumour has returned—a group with particularly short survival—the single-agent therapy could provide a last-line option where none currently exists. The trial is a dose-finding study, so its immediate impact will be to establish whether the approach is tolerable and at what dose, paving the way for larger efficacy trials.

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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 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. Following treatment, all participants will be followed for up to 5 additional years for safety, progression of disease and survival. Participants with newly diagnosed glioblastoma will undergo a baseline [68Ga]Ga-NeoB PET/CT or PET/MRI after the surgery/biopsy of the tumor.Participants with recurrent glioblastoma carry a dismal prognosis and a short survival. 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 in

Researchers

Shaveta Mehta (Principal Investigator)

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