A phase 3 multicenter study to evaluate the safety and efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in treatment of low-grade (LG) upper tract urothelial cancer (UTUC).

TPS4613 Background: Padeliporfin VTP is a combination product: drug, padeliporfin is administered IV and a device, a laser light delivery system, includes a source of light (the laser) that emits near-infrared (NIR) light at 753 nm, and optic fiber that delivers the light to the target lesion(s) in the upper tract urothelium. In Phase 1 NCT03617003 study 19 patients(pts) received up to 2 endoscopic VTP treatments with 6 mos follow-up(FU). Pts with residual or recurrent UTUC (high grade(HG)or LG) who failed prior endoscopic treatment/unable/unwilling to undergo surgery were included. Primary endpoint, Maximum tolerated dose (MTD) of laser light fluence, was identified using dose escalation model with a modified continual reassessment method with increasing light fluence (100-200 mW/cm). Secondary endpoint was efficacy, defined by absence of visible tumor and negative urine cytology 30 days post-treatment. 14(74%) pts received the MTD of 200mW/cm, 2 (11%) of whom experienced DLTs (flank pain grade 2 and 3). Response rate at 30 days was 94% (50% CR, 44% partial). 8 pts received 2nd VTP, with a final observed 68% complete response (CR) rate. Most frequent adverse events: transient flank pain (79%) and hematuria (84%). No treatment-associated ureteral strictures were reported. All patients had preserved kidney at the 6-mos FU(Wesley Yip,2022). Methods: Padeliporfin VTP is being evaluated in a phase 3 study in patients with UTUC LG,100 patients are planned to be enrolled. Enrollment started in Mar 2021 and is ongoing in USA, EU&Israel,3 pts are enrolled. Pts are being treated with padeliporfin VTP in two phases: Induction and Maintenance treatment Phases (ITP and MTP). ITP consists of 1-3 VTPs every 28 days. If CR is not achieved after 1 st VTP, up to 2 additional VTPs are allowed. If CR is achieved in the ITP, pts are allowed into the MTP (12 mos). In the MTP VTPs can be provided every 3 mos for pts with recurrent tumor that is deemed treatable, defined as LG with the largest tumor (index) 5 -15 mm, in up to 2 locations in the kidney or one ureter location ≤20 mm. Long Term FU Phase: Pts completing the MTP, will be followed for safety for 48 mos with no VTPs. Primary objective is to demonstrate efficacy and durability of effect of padeliporfin VTP treatment. Secondary objective-evaluation of padeliporfin VTP‐related safety and tolerability. Key inclusion criteria: Up to 2 biopsy-proven LG UTUC tumors with the largest tumor (index) 5-15 mm, located in the calyces, renal pelvis or in the ureter, with no HG cells. Ureter involvement in one location ≤ 20 mm. Key exclusion criteria: Current HG or muscle invasive urothelial bladder cancer . CIS current or previous in the upper urinary tract. History of ≥ T2 urothelial cancer in the past 2 years. DSMB last reviewed the trial in Sep 2022 and suggested the trial continue as planned. Clinical trial information: NCT04620239 .