Updated treatment results from a phase I study of WST11 phototherapy (VTP) for upper tract urothelial carcinoma

INTRODUCTION AND OBJECTIVE: The treatment of upper tract urothelial carcinoma (UTUC) presents technical challenges with endoscopic access and treatment delivery, representing a significant barrier to organ-preserving treatments in UTUC, limiting endoscopic management to small, low-grade tumors. Vascular-targeted photodynamic therapy (VTP) using intravascular photosensitizing agent padeliporfin (WST11) has demonstrated preclinical efficacy in preclinical animal models and provides an alternative to extirpative surgery in patients unable or unwilling to undergo extirpative surgery. Herein we present updated results from a phase 1 dose-finding study of WST11-VTP of the upper tract. METHODS: 18 patients with recurrent UTUC were treated with up to 2 sessions of endoscopic WST11-VTP. Eligibility included residual or recurrent urothelial carcinoma of the ureter or renal pelvis failing prior endoscopic treatment, who are unable or unwilling to undergo surgical management by resection of the involved ureter or kidney. A light dose escalation model was employed with increasing light fluence from 100mW/cm up to a maximally tolerated dose of 200mW/cm. The primary endpoint was the determination of maximally tolerated laser light fluence rate, with the secondary objective to evaluate treatment efficacy defined by absence of visible tumor and negative urine cytology following treatment. RESULTS: Complete response (CR) and tumor recurrence rates at 30 days after treatment were 67% and 28%, respectively. A second VTP treatment was performed in 8 (44%) patients, with 67% CR rate. The efficacy rates were comparable among patients who received the intermediate and highest light fluence and between the first and second treatment. Graded adverse events related to treatment are showed in table 1. No ureteral strictures were identified with the procedure. No evidence of increased toxicity was identified among patients who received a second VTP treatment. CONCLUSIONS: WST11-VTP shows promising evidence of therapeutic treatment effect in low- and high-grade upper tract urothelial tumors with limited treatment related toxicity. These early results provide support for further investigation to evaluate the curative potential for this therapy in a planned multicenter trial. (Table Presented).