69 NanoPac-2017-01 Mid-Study Report: Safety, Tolerability, and Preliminary Efficacy of Intracystic Submicron Particle Paclitaxel (SPP) for the Treatment of Mucinous Cysts

Abstract

INTRODUCTION: Pancreatic Mucinous cystic lesions (MCL) have significant potential for malignant transformation; delivery of SPP as a direct intratumoral injection confirmed SPP present at the delivery site for at least 100 days in a prior study; intracystic therapy with SPP may prevent progression to cancer without corresponding systemic toxicities. METHODS: Aim: To determine safety and preliminary efficacy of SPP for treatment of MCLs using endoscopic ultrasound Fine Needle Injection (EUS-FNI). Materials and Methods: Subjects with confirmed MCL, based on elevated intracystic CEA and cytology, receive intracystic SPP via EUS FNI at volumes equal to the aspirated cyst fluid volume in sequential cohorts at 6, 10, and 15 mg/mL in a standard “3+3” dose-escalation protocol. The highest dose with acceptable safety and tolerability profile, as determined by a DSMB, will proceed into the second phase of the study; 9 additional subjects will receive two injections of SPP (same dose) 12 weeks apart. Subjects are followed for 6 months for clinical endpoints including: safety and tolerability evaluations, physical examination findings and vital signs; pharmacokinetic analysis of systemic paclitaxel drug levels; and cyst volume response as reported by imaging at 3 and 6 months. RESULTS: Nine subjects have been enrolled to date; 5 have completed the study (1 injection). EUS, imaging, CEA and amylase concentration were consistent with branched duct IPMN cyst (BD-IPMN) or MCNs (Table 1). To date, no dose limiting toxicities, serious adverse events related to treatment, or clinically significant blood work (chemistry; hematology; coagulation) or urinalysis have been reported. Adverse events potentially related to SPP include mild, transient abdominal pain/discomfort in 4 subjects and nausea in 2 subjects. Systemic paclitaxel concentration did not exceed 1 ng/mL, and was undetectable at 2 weeks supporting retention of SPP at delivery site. Cyst volumes in 3 of 5 completed subjects reduced by month 6, 2 remained stable (Table 2). CONCLUSION: Intracystic SPP appears safe and tolerable when administered at 6, 10, and 15 mg/mL in a volume equal to that of aspirated cyst fluid. Minimal systemic study drug exposure is experienced. No patients developed pancreatitis. Intracystic SPP appears to prevent continued growth of the cysts and may reduce total cyst volume. Subject enrollment to the second phase (2 injections 12 weeks apart) is underway at 15 mg/mL.