Convection enhanced delivery of Rhenium (¹⁸⁶Re) Obisbemeda (¹⁸⁶RNL) in recurrent glioma: a multicenter, single arm, phase 1 clinical trial.

Abstract

Rhenium (¹⁸⁶Re) Obisbemeda (¹⁸⁶RNL), chelated-¹⁸⁶Re encapsulated in nanoliposomes and delivered to brain tumors via convection enhanced delivery (CED), was evaluated in a Phase 1 dose escalation trial (NCT01906385). The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included safety and tolerability, dose distribution, the overall response rate (ORR), disease-specific progression-free survival (PFS), and overall survival (OS). 21 patients received up to 22.3 mCi ¹⁸⁶RNL over 6 dosing cohorts. Most adverse events (AEs) were unrelated to ¹⁸⁶RNL and the MTD was not reached. Although not predefined outcomes, the mOS and mPFS were 11 and 4 months, respectively, and found to correlate with radiation absorbed dose to the tumor and percent tumor treated. When dichotomized by absorbed dose of 100 Gy, the mOS and mPFS were 17 months and 6 months, respectively, for >100 Gy, compared to 6 (mOS) and 2 (mPFS) months, respectively, for <100 Gy. For ORR, 57.1% exhibited stable disease (SD), 4.8% partial response, and 38.1% progressive disease. Overall, patients received radiation absorbed doses without significant toxicity higher than possible with external beam radiation therapy (EBRT) and demonstrated mOS beyond standard of care for recurrent glioblastoma (~8 months).