Phase 3 ENLIGHTED trial: Padeliporfin VTP shows promise in low-grade UTUC

Padeliporfin vascular targeted photodynamic (VTP) therapy demonstrated initial safety and efficacy in patients with low-grade upper tract urothelial carcinoma (UTUC), according to interim data from the phase 3 ENLIGHTED trial (NCT04620239), which will be presented at the 16th European Multidisciplinary Congress on Urological Cancers (EMUC 2024) in Lisbon, Portugal.¹

Recruitment for the ENLIGHTED trial remains ongoing.

According to the authors, “Padeliporfin VTP is a combination of padeliporfin administered IV and a laser light emitting near-infrared through an optic fiber delivering the light endoluminally to UTUC tumors.”

The ENLIGHTED trial is assessing the investigational therapy in patients with low-grade non-invasive UTUC in either the kidney or the ureter.

At the time of data cutoff (April 29, 2024), the study had treated 22 patients, with 14 of those having completed the induction treatment phase (ITP) of the trial. At the end of the ITP, 86% of patients (12/14) had achieved a complete response.

Padeliporfin also appeared to be well-tolerated. Adverse events (AEs) were primarily grade 1-2 and resolved within a few days. The most frequent treatment-related AEs were flank pain (16%), fatigue (8%), hematuria (8%), procedural pain (8%), vomiting (8%), nausea (6%), and dysuria (4%).

One patient in the study experienced a grade 3 treatment-related serious AE of renal colic, which was resolved within 3 days. No grade 4 or 5 serious AEs were observed. Overall, the safety profile of padeliporfin VTP was consistent with previous data from the phase 1 study (NCT03617003) of the investigational treatment.

“The overall profile and robustness of response to padeliporfin VTP underscores its potential to reshape the therapeutic landscape in patients with UTUC,” said lead author Gautier Marcq, MD, assistant professor of urology at Centre de Universitaire Régional Hospitalier de Lille, Lille, France, in a news release on the findings.² “Current standards of care in this indication often require an invasive surgical intervention, resulting in many cases in organ injury or loss, or a burdensome therapeutic regimen that fails to match surgery in efficacy. These results highlight padeliporfin VTP as a compelling alternative, which may not require patients to compromise between sparing their organs and treating their cancer. I am encouraged by these data and look forward to additional analyses towards improved treatment and better outcomes for patients with UTUC.”

In total, the open-label trial plans to enroll 100 adult patients with low-grade UTUC across centers in the United States, European Union, and Isreal. To be eligible for enrollment, patients must have up to 2 biopsy proven low-grade UTUC lesions with an index tumor of 15 mm or less in the kidney (or 20 mm or less in the ureter) as well as no evidence of high-grade cytology.

For the study, patients are treated in 2 phases: induction and maintenance treatment phases. In the induction phase, patients will receive 1 to 3 VTP treatments every 4 weeks until complete response or treatment failure. Complete response in the study is defined as the absence of disease based on absence of visual tumor on endoscopy, no evidence of tumor on biopsy, or negative urine cytology by instrumented collection.

If complete response is achieved, patients will progress to the maintenance phase, where they will be followed with endoscopic evaluation every 3 months. In this phase, patients with recurrent tumors up to 12 months will receive VTP. Patients who complete the maintenance phase will be followed for an additional 48 months to assess long-term outcomes.

The primary outcome measure for the study is complete response 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, which may be assessed for up to 12 months post primary response evaluation.³

Recruitment for the ENLIGHTED trial remains ongoing. According to the company, enrollment is expected to be complete by early 2025.

The authors note that the “results [are] expected to provide basis for approval of a new therapy that clinically benefits [patients].”

References

1. Marcq G, Kaufman R, Margulis V, et al. 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). Presented at: 16th European Multidisciplinary Congress on Urological Cancers. November 7-10, 2024. Lisbon, Portugal. Abstract P225

2. ImPact Biotech presents updated interim phase 3 data from ENLIGHTED study of padeliporfin VTP in low grade UTUC at EMUC 2024. News release. ImPact Biotech. Published online and accessed November 7, 2024. https://www.globenewswire.com/en/news-release/2024/11/07/2976523/0/en/ImPact-Biotech-Presents-Updated-Interim-Phase-3-Data-from-ENLIGHTED-Study-of-Padeliporfin-VTP-in-Low-Grade-UTUC-at-EMUC-2024.html

3. ENdoluminal LIGHT ActivatED Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) Study (UCM301). ClinicalTrials.gov. Last updated October 3, 2024. Accessed November 7, 2024. https://clinicaltrials.gov/study/NCT04620239