ENLIGHTED phase 3 study: Efficacy and safety of padeliporfin vascular targeted photodynamic therapy (VTP) for treatment of low-grade upper tract urothelial cancer (LG UTUC).
Authors: Margulis Vitaly , Kaufman Ronald P. , Marcq Gautier , Shore Neal D. , Colombel Marc , Uchio Edward M. , Psutka Sarah P. , Aller Marcos , Rausch Steffen , Raventos Carles , Shvero Asaf , Mroz Axelle , Kudinova Natalia , Cohen Yaniv , Krasnopolskaya Inna , Alpert Genia , Scherz Avigdor Joshua , Coleman Jonathan 
Published: June 2024

TPS4622

Background: Padeliporfin VTP has demonstrated safety and efficacy for UTUC treatment in a Phase 1 study (NCT03617003). Padeliporfin VTP is a combination product: a drug, padeliporfin administered IV; a device: a laser light delivery system/laser-source of light emitting near-infrared (NIR) light at 753nm; and an optic fiber delivering the light endoluminally to the vicinity of UTUC tumors within the collecting system. 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 from USA, EU and Israel. Key inclusion criteria is up to 2 biopsy-proven LG UTUC with index tumor ≤15mm in the kidney and≤20mm in the ureter with an absence of high-grade cells on cytology. VTP is performed via retrograde upper tract endoscopy under anesthetic and low light conditions, Padeliporfin is injected IV and a laser light diffuser fiber 20-40 mm is positioned in proximity of the tumor through the scope. After Padeliporfin injection, the laser fiber is illuminated for 10 min. The fiber can be repositioned to provide up to 3 treatments within the upper tract. 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. Patients achieving CR will proceed to the MTP and be followed with endoscopic evaluation every 3 months with VTP provided for recurrent tumors only up to 12 months. Patients with high-grade recurrences will be deemed treatment failures and removed from the study to standard of care treatment. Patients completing the MTP, will be followed for an additional 48 months for long-term outcomes. Primary outcome is CR on endoscopic evaluation and selective cytology at the time of primary response evaluation (28 ± 3 days post last treatment) during padeliporfin VTP ITP. A total of 100 patients are to be enrolled. As of 21 Jan 2024, 17 patients have been treated. 13 patients completed ITP and had CR 10/13 (77%) and PR 3/13 (23%). Patients baseline characteristics: age 67±12 years; gender: 9(53%) males and 8(47%) females; tumors location: 5(29%) in ureter, 13(76%) in the kidney; number of tumors: 7(41%) 2 tumors, 10(59%) 1 tumor. The most frequent treatment related adverse events were: flank pain 17%, vomiting 8%, fatigue 8%, nausea 6%, hematuria 6%, all Grade 1-2, resolved within few days. Grade 3 serious adverse events 9% (flank pain, hypertension, renal colic, urinary tract infection) were resolved within 2-7 days. To date Padeliporfin VTP has shown evidence of safety and efficacy with preliminary data that is consistent with prior experience. Recruitment for the ENLIGHTED trial is ongoing with results expected to provide basis for approval of a new therapy that clinically benefits pts. Clinical trial information: NCT04620239 .