NCT05739942

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

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

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

This study will investigate different doses of \[177Lu\]Lu-NeoB in combination with RT and TMZ in participants with newly diagnosed glioblastoma, with methylated or unmethylated promoter, to assess the safety and efficacy of \[177Lu\]Lu-NeoB in combination with the SoC and in recurrent glioblastoma as single agent, 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.

Detailed description

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. 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. Recurrent glioblastoma: 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 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. \[177Lu\]Lu-NeoB will be administered as a single dose every 3 weeks (Q3W) for 6 administrations. Up to 4 additional administrations of \[177Lu\]Lu-NeoB may be considered if participants tolerate and benefit from \[177Lu\]Lu-NeoB (total up to 10 dose administrations).

Conditions

• Newly Diagnosed and Recurrent Glioblastoma

Interventions

Type	Name	Description
DRUG	[177Lu]Lu-NeoB	Radiopharmaceutical solution for infusion
DRUG	[68Ga]Ga-NeoB	Either provided as Kit for the radiopharmaceutical preparation of \[68Ga\]Ga-NeoB or as ready to use radiopharmaceutical solution for injection
OTHER	Temozolomide	Capsules/ lyophilized powder in single-dose vial for reconstitution.

Timeline

• Start date: 2024-05-15
• Primary completion: 2026-12-10
• Completion: 2032-07-01
• First posted: 2023-02-22
• Last updated: 2026-02-03

Locations

23 sites across 8 countries: United States, France, Germany, Israel, Italy, Portugal, Spain, United Kingdom

Regulatory

• FDA-regulated drug study