Phase 3 trial of padeliporfin VTP completes treatment in LG-UTUC

Investigators have completed treatment of all patients in the phase 3 ENLIGHTED trial evaluating padeliporfin vascular-targeted photodynamic therapy (VTP) in patients with low-grade upper tract urothelial carcinoma (LG-UTUC), according to an announcement from ImPact Biotech.

The company reported that 91 patients have been treated and that interim data from the study are planned for presentation at the 2026 European Society for Medical Oncology (ESMO) Congress in October. ImPact Biotech also reported receiving written feedback from the FDA following a pre–new drug application (NDA) meeting in April 2026, stating that the agency acknowledged potential clinical meaningfulness of durable complete responses in the treated area, supporting a regulatory pathway toward NDA submission in 2027.

ENLIGHTED evaluates padeliporfin VTP in LG-UTUC

ENLIGHTED (NCT04620239) is an open-label, single-arm, non-randomized phase 3 study being conducted in the US, Europe, and Israel. The trial enrolled patients with low-grade, noninvasive UTUC involving the kidney or ureter. Eligible patients could have newly diagnosed or recurrent disease, with up to 2 biopsy-confirmed low-grade lesions and no high-grade cells on instrumented cytology. Tumor-size criteria included lesions of 5 mm to 15 mm in the kidney or 5 mm to 20 mm in the ureter.

The treatment consists of an induction treatment phase followed by a maintenance phase. During induction, patients receive 1 to 3 padeliporfin VTP treatments at 4-week intervals or until a complete response (CR) is achieved. During the maintenance phase, standard-of-care treatment is administered alongside VTP therapy every 3 months for up to 12 months. Across these phases, padeliporfin is administered intravenously, followed by VTP therapy via a ureteroscopy with laser fiber illumination for 10 minutes in the proximity of the tumor.

The trial's primary end point is the response rate at the end of the induction treatment phase. Secondary end points include safety, tolerability, and duration of response.

Initial results from the trial were presented at the 2026 American Society of Clinical Oncology Annual Meeting, which included 78 enrolled patients and 63 patients who had completed induction as of January 19, 2026.² The reported CR rate at primary response evaluation was 73%, while 17.7% had a partial response, 3.2% had durable response, 4.8% had progressive disease, and 1.6% had stable disease.

Among patients with a CR who had completed maintenance at the data cutoff, 88.2% maintained CR in the treated area for at least 12 months. The median duration of response had not been reached and was at least 23.9 months.

Safety findings from that analysis were preliminary. The most frequently reported treatment-emergent adverse events included hematuria (10.6%), flank pain (8.6%), nausea (5.5%), procedural pain (4.5%), abdominal pain (4.1%), dysuria (4.1%), vomiting (3.4%), and fatigue (3.1%), all reported as grade 1 or 2. Twenty-three (7.7%) serious adverse events were reported, most of which were considered unrelated to treatment. One grade 3 serious adverse event, renal colic attributed to VTP, resolved within 2 days.

Additional results from the study will be presented atESMO in October. The company also reported that they are in discussion with the FDA regarding a potential expanded access program to expand patient reach and support real-world clinical use of padeliporfin VTP in the US.

REFERENCES

1. Treatment in phase 3 ENLIGHTED trial of Padeliporfin VTP in LG-UTUC and positive regulatory updates. News release. ImPact Biotech. September 9, 2026. Accessed September 10, 2026. https://www.globenewswire.com/news-release/2026/09/09/3358733/0/en/impact-biotech-announces-completion-of-treatment-in-phase-3-enlighted-trial-of-padeliporfin-vtp-in-lg-utuc-and-positive-regulatory-updates.html

2. Margulis V, Kaufman Jr. R, Raman JD, et al. Advancing treatment of low-grade upper tract urothelial carcinoma (LG UTUC) with padeliporfin vascular-targeted photodynamic therapy (VTP): The ENLIGHTED phase 3 trial. J Clin Oncol. 44, 2026 (suppl 16; abstr TPS4643). doi:10.1200/JCO.2026.44.16_suppl.TPS4643