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).
This is an open-label phase 3 study conducted in USA, EU, and Israel. Key inclusion criteria: up to 2 biopsy‑proven LG UTUC with index tumor ≤15 mm (kidney) or ≤20 mm (ureter) and absence of high‑grade cells on instrumental cytology. VTP is performed via retrograde upper‑tract endoscopy under anesthesia 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.
As of 19 October 2025, 68 pts had been treated and 61 completed ITP. Response rates were: CR 71.6%, PR 15.0%, DR 6.7%, PD 5.0%, and stable disease 1.7%. By the 19 October 2025 cut‑off date, only 35% of pts with CR on PRE had completed MTP and 92.9% had sustained CR in the treated area (TA) for ≥12 mos. Median Duration of Response (DOR) in the TA was not reached and is ≥ 24 mos. Most pts were still ongoing in MTP/follow-up. The most frequent treatment‑emergent adverse events (TEAEs) were hematuria 11.6%, flank pain 9.3%, nausea 5.6%, procedural pain 4.9%, abdominal pain 4.1%, vomiting 3.7%, dysuria 3.4%, and fatigue 3.4% (all Grade 1–2, median duration 5 days). 21 (7.7%) serious adverse events (SAE) occurred in 16 pts (23.5%), most were unrelated to treatment. One patient experienced a Grade 3 SAE (renal colic related solely to VTP), it resolved within 2 days.
Padeliporfin VTP demonstrated a favorable preliminary safety and efficacy profile consistent with prior experience. Recruitment is ongoing and final outcomes are expected to support regulatory approval of an organ‑preserving therapy for LG UTUC.
Steba/Impact biotech