ENLIGHTED phase 3 study: Interim results of efficacy and safety of padeliporfin vascular targeted photodynamic therapy (VTP) in the treatment of low-grade upper tract urothelial cancer (LG UTUC).

LBA4513 Background: Padeliporfin VTP has demonstrated safety and efficacy for UTUC treatment in a Phase 1 study (NCT03617003). Padeliporfin VTP is a combination product of a drug, padeliporfin administered IV and a optical fiber coupled laser emitting near-infrared light endoluminally to UTUC tumors. We report the interim analysis of efficacy and safety outcomes of Padeliporfin VTP for treatment of LG UTUC in ENLIGHTED, a Phase 3 trial (NCT04620239). Methods: This is an open-label phase 3 study conducted in USA, EU, and Israel. Key inclusion criteria are: up to 2 biopsy-proven LG UTUC with index tumor ≤15mm in the kidney (≤20mm in the ureter) and absence of high-grade cytology. VTP is performed via retrograde upper tract endoscopy under anesthetic and low light conditions, Padeliporfin is injected IV and an optical fiber, 20-40 mm diffuser, is positioned in proximity of the tumor through the scope. After Padeliporfin injection, the laser is activated for 10 min. Patients (Pts) are treated in two phases: Induction (ITP) and Maintenance Treatment Phases (MTP). ITP consists of 1-3 VTPs provided at 4-week intervals until achieving complete response (CR) or treatment failure on Primary Response Evaluation (PRE) visit. Primary endpoint is CR on endoscopic evaluation and negative instrumental cytology at the time of PRE (28 ± 3 days post last treatment) during ITP. Pts achieving CR will proceed to MTP and be followed with endoscopic evaluation every 3 months (mos) with VTP provided for recurrent tumors in the period up to 12 mos. Pts completing MTP, will be followed for additional 48 mos for long-term outcomes. A total of 100 pts are to be enrolled. Results: Interim analysis is defined in the study protocol and conducted mid-way (50% of evaluable pts) into the study with the cut-off date 5 November 2024. CR rate 73%, Partial Response rate 13.5%, Disease Recurrency rate 10.8%, Disease progression rate 2.7%, Overall Response Rate 86.5%. The most frequent TEAEs (Grade 1-2, resolved within few days) were: hematuria 14%, flank pain 10%, procedural pain 6.4%, dysuria 5.2%, UTI 5.2%, abdominal pain 4.7%, vomiting 4.7%, fatigue 4%, nausea 3.5%. Sixteen (9.2%) Grade 3 serious adverse events (SAE) were reported. Grade 3 SAEs related to the VTP treatment were renal colic and flank pain, and resolved within 2 days. Conclusions: Padeliporfin VTP has demonstrated efficacy and safety aligned with previous findings. Recruitment in ENLIGHTED trial is ongoing, with results anticipated to support the approval of a new therapy offering clinical benefits and organ-sparing alternative for pts. Clinical trial information: NCT04620239 .