TIP-22. Trial in progress: A Phase Ib dose-finding study and evaluation of [177Lu]Lu-NeoB plus radiotherapy and temozolomide for newly diagnosed glioblastoma and as a single agent for recurrent glioblastoma

The current standard of care (SOC) for newly diagnosed glioblastoma includes surgery followed by radiotherapy plus temozolomide. Although this SOC was established 20 years ago, there has been little progress in the development of new therapies that improve patient survival. Furthermore, there is no defined SOC for recurrent glioblastoma. [177Lu]Lu-NeoB is a radiolabeled peptide with high affinity for gastrin-releasing peptide receptor (GRPR). GRPR is highly expressed in glioblastoma and has been identified as a potential new therapeutic target. This single arm, Phase Ib, open-label, dose-finding study in two parallel groups (NCT05739942) will evaluate [177Lu]Lu-NeoB plus radiotherapy and temozolomide for newly diagnosed glioblastoma and as a single agent for patients with recurrent glioblastoma. Up to 48 patients (aged ≥18 years) will be enrolled: 27 in Group 1 (newly diagnosed glioblastoma) and 21 in Group 2 (glioblastoma at first or second recurrence). PET imaging with [68Ga]Ga-NeoB will take place at screening; tumor uptake is required in Group 2 only. Dose escalation will follow the Bayesian Optimal Interval approach, with consecutive cohorts of 3–6 evaluable patients. In Group 1, patients will receive [177Lu]Lu-NeoB Q4W (starting dose plus three provisional dose levels) plus concomitant radiotherapy and temozolomide, followed by temozolomide maintenance. In Group 2, patients will receive [177Lu]Lu-NeoB Q3W (starting dose plus two provisional dose levels) as a single agent. In both groups, six [177Lu]Lu-NeoB administrations are planned. The dose-limiting toxicity (DLT) period after the first administration of [177Lu]Lu-NeoB is 8 weeks for Group 1 and 6 weeks for Group 2. The primary endpoint is the incidence and nature of DLTs with the aim to identify the recommended doses of [177Lu]Lu-NeoB for newly diagnosed and recurrent glioblastoma. Secondary endpoints include safety, dosimetry, and pharmacokinetics of [177Lu]Lu-NeoB (in combination and as a single agent), progression-free survival (modified RANO criteria), and overall survival.