DDEL-22. Safety, feasibility, and preliminary efficacy of albumin-bound paclitaxel as monotherapy and in combination with carboplatin delivered by blood-brain barrier opening using a skull-implantable ultrasound: Preliminary results of a Phase I-II trial in recurrent glioblastoma

Abstract BACKGROUND We previously established the safety of administration of either carboplatin or albumin-bound paclitaxel (ABX) in conjunction with blood-brain barrier (BBB) opening by low-intensity pulsed ultrasound with microbubbles (LIPU/MB) using an implantable device (Sonocloud-9) (NCT03744026, NCT04528680). We demonstrated a multiple-fold increase in non-enhancing brain parenchymal levels of ABX and carboplatin by LIPU/MB, and prolonged carboplatin retention in the brain parenchyma after sonication. We have now evaluated ABX plus carboplatin delivered by LIPU/MB. METHODS We conducted a phase II clinical trial to deliver carboplatin (AUC 5) and ABX (260 mg/m2) in conjunction with BBB opening by LIPU/MB for treatment of first recurrence of glioblastoma (GBM) (NCT04528680). 35 patients were enrolled and evaluable. Endpoints included safety and tolerability, tumor growth rate (TGR), defined by volumetric measurements of contrast enhancement in sonicated regions in disease evaluation MRI, progression-free (PFS), and overall survival (OS). Patients with the first GBM recurrence of the Phase I trial were included for comparisons (n=16). RESULTS Main toxicity was myelosuppression, primarily uncomplicated and short-lived grade 4 neutropenia. PFS of patients treated with the combination regimen was significantly longer compared to that of patients treated with single-agent ABX (median PFS of 3.8 months vs 2.8 months, Log-rank p=0.02). Negative TGR exhibited prolonged OS (median OS 14.4 months) compared to positive TGR (median OS 8.4 months) in patients treated with ABX as monotherapy or combined with carboplatin (Log-rank p=0.03, n=43). By November 2025, data will be mature for a preliminary comparison of OS. CONCLUSIONS Delivery of ABX plus carboplatin using LIPU/MB is well-tolerated. TGR in sonicated brain appears to predict OS in patients treated with ABX with or without carboplatin delivered by LIPU/MB. Early signs of efficacy suggest that this combination might be superior to ABX monotherapy. Additional studies are necessary to confirm this observation.