397 A phase I/II trial of intracerebroventricular 177Lu DTPA omburtamab radioimmunotherapy for leptomeningeal metastasis from solid tumors

Background Leptomeningeal metastasis (LM) from solid tumors may be diagnosed in approximately 10% of patients with metastatic cancer and can occur virtually all malignant tumors. Median overall survival (OS) is poor limited to a few months LM-directed treatment, including available targeted therapy, immunotherapy radiation therapy. Omburtamab specifically binds B7-H3 (CD276), transmembrane glycoprotein the immunoglobulin superfamily. The expression on normal cells, brain, combined broad various types tumors, makes target for radioimmunotherapy LM In this first-in-human trial safety efficacy intracerebroventricular administration radiolabeled omburtamab, 177Lu-DTPA-omburtamab, will evaluated ductal or lobular breast cancer, non-small cell lung melanoma. Methods This an open-label phase I/II study. Part 1 dose-escalation conducted at ~4 sites (US/Europe) primary objective identifying maximum tolerated dose and/or recommended II 2 (RP2D). It follow 3+3 design pts receiving up five 5-week cycles 177Lu-DTPA-omburtamab. cohort-expansion ~9 which 48 3 cohorts (ductal [cohort A], B], melanoma C]) 16 each receive 5 week treatment 177Lu DTPA omburtamab RP2D determined 1. establish repeat doses 177Lu-omburtamab. Additional objectives Parts 1/2 include evaluation absorbed doses, PK profile, investigator-assessed response, duration progression-free survival, OS. Key inclusion criteria diagnosis either recurrent refractory LM; prior standard care leptomeningeal disease; acceptable hematological, liver kidney status; life expectancy >2 months. study has been approved by institution’s ethics board, provided informed consent before taking part. Trial Registration NCT04315246 Ethics Approval