TIP-17. LU-TARGET: A Phase 1 Study of Lutetium-177-PSMA-617 Adjuvant Radiotherapy for IDH wild type Gliomas Expressing PSMA following standard Treatment

BACKGROUND Prostate specific membrane antigen (PSMA)-directed therapeutics have revolutionized treatment of metastatic prostate cancer. However, this target is expressed by numerous tumor types. Given potential for strong PSMA expression within glioma neovasculature, we are exploring a PSMA-anchored adjuvant theranostic strategy incorporating PSMA PET imaging and radiopharmaceutical therapy (RPT) for malignant glioma neovessels and microscopic disease. MATERIALS/METHODS This is a phase I, trial-in-progress of adjuvant [177Lu]Lu-PSMA-617 for newly diagnosed, isocitrate dehydrogenase (IDH) wildtype gliomas following upfront standard-of-care temozolomide and external beam radiotherapy (EBRT). The primary outcome is safety, and primary endpoint is descriptive toxicity up to 8 weeks post first infusion of [177Lu]Lu-PSMA-617. Eligible patients have IDH1-R132H wildtype grade II-IV glioma with immunohistochemistry confirmation of PSMA expression. Eligible patients undergo screening [68Ga]Ga-PSMA-PET/MR scan performed 2 weeks post-EBRT. If PSMA avidity exceeds background brain parenchyma, the patient will receive 2 cycles of 7.4GBq of [177Lu]Lu-PSMA-617 spaced 4 weeks apart, in combination with standard adjuvant temozolomide (150-200 mg/m2 per cycle). Dosimetric assessment will be performed during the first cycle of [177Lu]Lu-PSMA-617 RPT, including serial single photon emission CT (SPECT) imaging of the head. Four weeks post-cycle 2, patients will undergo repeat [68Ga]Ga-PSMA-PET/MR. If residual PSMA avidity above background, patients can receive up to 4 additional monthly cycles of [177Lu]Lu-PSMA-617 spaced 4 weeks apart, in combination with standard adjuvant temozolomide. Patients will undergo regular safety assessments, frequent bloodwork, quality of life surveys and imaging every 2mo. A second [68Ga]Ga-PSMA-PET scan will be performed at progression. DISCUSSION/CONCLUSION This phase I study offers a novel approach to integrate RPT for a disease with substantial unmet need. The trial is undergoing IRB approval and slated to open in the next month. At the conference, we will share study design details and early patient experience/data.