Padeliporfin Vascular Targeted Photodynamic Therapy Safely Produces High Response Rates in Low-Grade Upper Tract Urothelial Cancer

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Padeliporfin (Tookad) vascular targeted photodynamic therapy is safe and effective for the treatment of patients with low-grade upper tract urothelial cancer (UTUC), according to data from the phase 3 ENLIGHTED trial (NCT04620239) presented during the 2025 ASCO Annual Meeting.1

At the November 5, 2024, data cutoff, efficacy-evaluable patients who received padeliporfin (n = 37) achieved an overall response rate of 86.5%, including a complete response (CR) rate of 73%. Disease recurrence occurred in 10.8% of patients and 2.7% experienced disease progression.

“Photodynamic therapy in this patient population seems to be effective, based on this interim analysis,” Vitaly Margulis, MD, the Paul C. Peters, MD, Chair in Urology and a professor of urology at The University of Texas Southwestern Medical Center in Dallas, said during the presentation.1 “The safety profile [of the treatment] was excellent, and I believe we may have another tool in our toolbox [that will] allow patients to maintain their kidney function and preserve their organs.”

Padeliporfin vascular targeted photodynamic therapy is a photosensitizing drug and light delivery system. Padeliporfin is administered intravenously, and a laser light delivery system emits near-infrared light while an optic fiber delivers the light to the target lesions. Following light activation, the drug produces a cascade of pathophysiological events that affect tumor vasculature.

ENLIGHTED Study Design and Baseline Characteristics

ENLIGHTED was a global, pivotal, single-arm study that enrolled patients with newly diagnosed or recurrent, low-grade, noninvasive UTUC. Eligible patients needed to have up to 2 low-grade, biopsy-proven tumor lesions of 5 to 15 mm in the kidney or 5 to 20 mm in the ureter on the ipsilateral side, and an absence of high-grade cells on instrumental cytology. Patients with high-grade or muscle-invasive urothelial carcinoma of the bladder, current or prior carcinoma in situ in the upper urinary tract, a history of invasive stage T2 or higher urothelial cancer within 2 years of enrollment, or photosensitive skin diseases or porphyria were excluded.2

Following screening and biopsy/cytology, all patients received padeliporfin at 3.66 mg/kg over 10 minutes, and each target area was then illuminated for 10 minutes.1,2 Patients received 1 to 3 padeliporfin vascular targeted photodynamic therapy treatments approximately 4 weeks apart. Following the primary response evaluation, patients who did not achieve a CR received standard-of-care therapy.

The primary end point was the number of patients achieving a CR, defined as the absence of UTUC tumors in the ipsilateral kidney and ureter during the primary response evaluation, which was 28 days plus/minus 3 days after up to 3 treatments during the padeliporfin vascular targeted photodynamic therapy induction phase. Secondary end points included duration of response (DOR) at the entire ipsilateral kidney, DOR at the treatment area of the ipsilateral kidney, overall renal function, kidney loss or preservation, and safety.2

Safety Data

In terms of safety, the most frequent adverse effects (AEs) were grade 1 or 2 in severity and resolved within a few days.1 The most common any-grade AEs included hematuria (14%), flank pain (10%), procedural pain (6.4%), dysuria (5.2%), urinary tract infection (5.2%), abdominal pain (4.7%), vomiting (4.7%), fatigue (4%), and nausea (3.5%). Grade 3 serious AEs occurred at a rate of 9.2%. Grade 3 serious AEs related to therapy consisted of renal colic and flank pain; these events resolved within 2 days.

“Recruitment [in ENLIGHTED] will continue and will hopefully result in an approval,” Margulis said.1

References

1. Margulis V, Kaufman RP, Marcq G, et al. ENLIGHTED phase 3 study: interim results of efficacy and safety of padeliporfin vascular targeted photodynamic therapy (VTP) in the treatment of low-grade upper tract urothelial cancer (LG UTUC). J Clin Oncol. 2025;43(suppl 17):LBA4513. doi:10.1200/JCO.2025.43.17_suppl.LBA4513
2. ENdoluminal LIGHT ActivatED treatment of upper tract urothelial cancer (ENLIGHTED) study (UCM301). ClinicalTrials.gov. Updated February 7, 2025. Accessed July 1, 2025. https://clinicaltrials.gov/study/NCT04620239