Updated interim results from the phase 3 ENLIGHTED trial (NCT04620239) indicate that padeliporfin vascular targeted photodynamic (VTP) therapy maintains a high complete response (CR) rate and a tolerable safety profile in patients with low-grade upper tract urothelial cancer (UTUC). The data, presented at the 16th European Multidisciplinary Congress on Urological Cancers, suggest that padeliporfin VTP could offer a compelling alternative to current standards of care, which often involve invasive surgical interventions.
Efficacy and Safety Data
The trial data showed that the CR rate with padeliporfin VTP was 86% among evaluable patients with low-grade UTUC who completed the induction treatment phase (n = 14). The treatment was well-tolerated, with a safety profile consistent with prior data. Most adverse effects (AEs) were grade 1/2 and primarily pain-related, resolving within 2 to 7 days. One patient experienced a grade 3 serious AE (SAE) related to VTP therapy, which resolved within 2 days. No grade 4/5 SAEs were observed.
Expert Commentary
Gautier Marcq, MD, an ENLIGHTED investigator, noted the potential of padeliporfin VTP to reshape the therapeutic landscape in UTUC. He stated that current standards of care often require invasive surgery, leading to organ injury or loss, or burdensome therapeutic regimens that may not match surgery in efficacy. He expressed optimism about padeliporfin VTP as a compelling alternative that may allow patients to avoid compromising between organ sparing and cancer treatment.
ENLIGHTED Trial Details
Padeliporfin VTP combines an intravenously delivered photosensitizing drug and a laser light delivery system. The laser emits near-infrared light, delivered via an optic fiber to target lesions in the upper tract urothelial. The light activates padeliporfin, triggering pathophysiological events affecting tumor vasculature, resulting in tumor ablation and antitumor immunity.
The single-arm, non-randomized, open-label trial evaluates padeliporfin VTP in adult patients with new or recurrent low-grade, non-invasive UTUC of the kidney or ureter. Patients must have no more than 2 biopsy-proven tumor lesions of low-grade involvement, with the largest index tumor between 5 mm to 15 mm in diameter, located in the calyces, renal pelvis, or ureter of the ipsilateral kidney, and with an absence of high-grade cells on cytology.
The study includes induction and maintenance treatment phases. Patients in both phases receive intravenous padeliporfin followed by VTP therapy via outpatient endoscopy. The induction phase involves 1 to 3 VTP therapy treatments at 4-week intervals or until a CR is achieved. Patients proceeding to the maintenance phase receive standard of care treatment alongside VTP therapy every 3 months for up to 12 months.
The primary objective is to assess response rates and durability with padeliporfin VTP at the end of the induction phase. The secondary objective is to evaluate the regimen’s safety and tolerability.
Previous Data and Trial Status
Preliminary efficacy and safety data from ENLIGHTED were previously presented at the 2024 ASCO Annual Meeting. As of January 21, 2024, the CR and PR rates were 77% and 23%, respectively, among 13 evaluable patients who completed their second visit. Common grade 1/2 treatment-related AEs included flank pain (17%), vomiting (8%), fatigue (8%), nausea (6%), and hematuria (6%). Grade 3 SAEs occurred in 9% of patients.
Recruitment for the ENLIGHTED study is ongoing, with a planned enrollment of 100 patients at 29 sites across the United States, European Union, and Israel. Trial enrollment is expected to conclude by early 2025. As of the April 29, 2024, data cutoff for the current analysis, 22 patients had begun treatment.
Eyal Morag, MD, chief medical officer of ImPact Biotech, expressed encouragement regarding the consistent patient responses to padeliporfin VTP treatment. He anticipates that subsequent data updates will provide the basis for registration of padeliporfin VTP in low-grade UTUC and plans to replicate the effect in other unresectable solid tumors, starting with a phase 1 study in pancreatic ductal adenocarcinoma.
