ENdoluminal LIGHT ActivatED Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) Study

This is a phase 3, open label, single arm study of padeliporfin in the treatment of Upper Tract Urothelial Carcinoma (UTUC). The ENLIGHTED study will recruit patients with low-grade non-invasive upper tract urothelial carcinoma in either the kidney or the ureter. Patients will be treated with padeliporfin VTP in two phases: an Induction Treatment Phase and a Maintenance Treatment Phase and will be followed up for up to an additional 48 months in the long term (non intervention) follow up phase with the specific duration depending on the patient's response to treatment

Induction Treament Phase: Patients entered in the study will undergo an induction treatment phase consisting of 1-3 padeliporfin VTP treatments provided 4 weeks (28 +/-3 days) apart. The goal of this induction treatment phase will be to achieve Complete Response (CR) in the involved ipsilateral tract system. During this phase, patients will be treated with padeliporfin VTP to visually identified tumor sites in the calyces, renal pelvis and/or ureter and subsequently examined endoscopically at 28 +/- 3 days post treatment to determine whether the treatment was successful. If CR is not achieved, an additional two treatments of padeliporfin VTP are permitted 28 +/- 3 days apart for a total of up to 3 treatments during the induction treatment phase. The Primary Response Evaluation (PRE) will be performed 28 +/- 3 days after the last VTP treatment, to determine if the treatment was successful at achieving CR defined as: absence of visible tumor on endoscopy, negative urinary cytology by instrumented collection, and no evidence of tumor on biopsy (if feasible). Patients undergoing extirpative surgery of any part of the ipsilateral kidney or ureter for indications related to urothelial cancer will be considered as no longer having CR. If CR is not achieved after 3 treatments with padeliporfin VTP the treatment will be considered unsuccessful and the patient will be discontinued from the Treatment Phases.

Maintenance Treatment Phase: Patients achieving CR at the induction treatment phase will be allowed into the maintenance treatment phase of the study. The patients will then be followed over a period of 12 months post PRE, to assess the duration of response and its safety, and to provide planned maintenance treatment.

Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence that is deemed treatable as defined by the following criteria: low-grade tumors with the largest tumor (index tumor) betwen 5 mm and 15 mm in diameter, in up to 2 anatomical locations in the calyces, renal pelvis or the ureter with ureter involvement in one anatomical location with no more than 20 mm of contiguous ureteral length). Patients with treatable tumor recurrence post Induction Treatment Phase would be considered as no longer having 'complete response in the entire ipsilateral kidney' and time to recurrence will be recorded. Patients undergoing extirpative surgery of any part of the ipsilateral kidney or ureter for indications related to urothelial cancer will be considered as no longer having CR and time to this event will be recorded.

Long Term Follow-up Phase: Patients completing the 12 months of the maintenance treatment phase of the study, could be followed for an additional 48 months to monitor for disease related outcomes and VTP treatment related adverse events with the specific duration depending on the patient's response to treatment. No additional padeliporfin VTP treatment will be administered during this phase. Patients completing the maintenance phase of the study who are in CR in V3 will undergo additional assessments 18 and 24 months (+/- 1 month) post-PRE and annually thereafter and for up to 5 years post PRE or until recurrence, progression, death or loss to follow up, to document safety and ongoing response.