Introduction:

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 an optical fiber coupled laser emitting near-infrared light endoluminally to UTUC tumors. We report the preliminary 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 theureter) 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  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. Patients achieving CR will proceed to MTP and be followed with endoscopic evaluation every 3 months  with VTP provided for recurrent tumors in the period up to 12 months. Patients completing MTP, will be followed for additional 48 months for long-term outcomes. A total of 100 patients are to be enrolled. As of 28 July 2025, out of the 68 patients  treated, 50 patients completed ITP. The CR rate is 70% (35), PR rate is 18% (9), DR rate is 10% (5), PD rate is 2% (1).  18 % of  patients have completed MTP and all sustained CR in the treated area for ≥12 months. The most frequent treatment emerged adverse events (TEAE)  were: hematuria 11.6%, flank pain 9.7%, nausea 5.8%, procedural pain 4.6%, abdominal pain 4.3%, vomiting 3.9%, dysuria 3.5%, fatigue 3.5%, UTI 2.3%, all Grade 1-2, resolved within few days. 19 (7.3%) serious adverse events (SAE) are reported. One patient experienced a Grade 3 SAE (renal colic related solely to VTP), which resolved within 2 days. Padeliporfin VTP has demonstrated a favorable safety and efficacy profile, with preliminary results consistent with prior clinical experience. Recruitment for the ENLIGHTED Phase 3 trial is ongoing. The final study outcomes are expected to support regulatory approval of a novel, organ-preserving therapy for patients with LG UTUC.

Results:

Conclusion:

Funding: Steba/Impact biotech