Interim results from the phase 3 ENLIGHTED trial indicate that padeliporfin vascular targeted photodynamic (VTP) therapy is a safe and effective treatment for patients with low-grade upper tract urothelial carcinoma (UTUC). The data, presented at the 16th European Multidisciplinary Congress on Urological Cancers (EMUC 2024), suggest that this novel therapy could offer a kidney-sparing alternative to more invasive surgical procedures.
Promising Efficacy Data
The ENLIGHTED trial (NCT04620239) is a single-arm, open-label study evaluating padeliporfin VTP in patients with low-grade, non-invasive UTUC affecting either the kidney or ureter. As of April 29, 2024, 22 patients had been treated, with 14 completing the induction treatment phase (ITP). An impressive 86% (12/14) of these patients achieved a complete response at the end of the ITP.
Complete response was defined as the absence of visual tumor on endoscopy, no evidence of tumor on biopsy, and negative urine cytology by instrumented collection.
Safety and Tolerability
Padeliporfin VTP also demonstrated a favorable safety profile. Adverse events (AEs) were primarily grade 1-2 and resolved within a few days. The most frequently reported treatment-related AEs included flank pain (16%), fatigue (8%), hematuria (8%), procedural pain (8%), vomiting (8%), nausea (6%), and dysuria (4%). One patient experienced a grade 3 treatment-related serious AE of renal colic, which resolved within 3 days. No grade 4 or 5 serious AEs were observed.
The ENLIGHTED Trial Design
The ENLIGHTED trial aims to enroll 100 adult patients with low-grade UTUC across multiple centers in the United States, European Union, and Israel. Eligible patients must have up to two biopsy-proven low-grade UTUC lesions, with an index tumor ≤15 mm in the kidney (or ≤20 mm in the ureter), and no evidence of high-grade cytology.
The trial consists of two phases: induction and maintenance. During the induction phase, patients receive one to three VTP treatments every four weeks until a complete response is achieved or treatment failure is determined. Patients achieving a complete response progress to the maintenance phase, where they are followed with endoscopic evaluation every three months. Patients with recurrent tumors during the 12-month maintenance phase are eligible to receive VTP. Following the maintenance phase, patients are followed for an additional 48 months to assess long-term outcomes.
The primary outcome measure is the complete response rate on endoscopic evaluation and selective cytology at the primary response evaluation (28 ± 3 days post last treatment) in the induction phase. Secondary outcome measures include duration of response, overall renal function, and safety, assessed for up to 12 months post primary response evaluation.
Expert Commentary
Dr. Gautier Marcq, assistant professor of urology at Centre de Universitaire Régional Hospitalier de Lille, commented on the findings, stating, "The overall profile and robustness of response to padeliporfin VTP underscores its potential to reshape the therapeutic landscape in patients with UTUC... These results highlight padeliporfin VTP as a compelling alternative, which may not require patients to compromise between sparing their organs and treating their cancer."
Implications for UTUC Treatment
UTUC is a relatively rare cancer, and current treatment standards often involve invasive surgical interventions that can result in organ injury or loss. Padeliporfin VTP offers a potential kidney-sparing approach, addressing a significant unmet need in the management of low-grade UTUC. Recruitment for the ENLIGHTED trial is ongoing, with completion expected by early 2025. The results are anticipated to provide the basis for potential regulatory approval of padeliporfin VTP, offering a new treatment option for patients with low-grade UTUC.
