Padeliporfin VTP Maintains Robust Responses and is Safe in Low-Grade Upper-Tract Urothelial Cancer

Padeliporfin vascular targeted photodynamic (VTP) therapy maintained a high complete response (CR) rate and a tolerable safety profile in patients with low-grade upper tract urothelial cancer (UTUC), according to updated interim results from the phase 3 ENLIGHTED trial (NCT04620239).¹

The data, which were presented at the 16th European Multidisciplinary Congress on Urological Cancers, 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).

Regarding safety, with additional follow-up in the maintenance treatment phase, the treatment was well-tolerated and had a safety profile consistent with prior data. The majority of adverse effects (AEs) were grade 1/2 and were primarily pain related. All AEs resolved within 2 to 7 days. Notably, 1 patient experienced a grade 3 serious AE (SAE), which was deemed related to treatment with VTP therapy; this resolved within 2 days. No grade 4/5 SAEs were observed.

“The overall profile and robustness of response to padeliporfin VTP underscores its potential to reshape the therapeutic landscape in patients with UTUC,” Gautier Marcq, MD, assistant professor in the Urology Department at the Centre de Universitaire Régional Hospitalier de Lille, Lille, France, and an ENLIGHTED investigator, stated in a news release. “Current standards of care [SOC] 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.”

ENLIGHTED Trial Overview

Padeliporfin VTP is a combination of an intravenously delivered photosensitizing drug and a laser light delivery system.² The laser emits near-infrared light, delivered by an optic fiber to target lesions in the upper tract urothelial. padeliporfin is then activated by the light, triggering several pathophysiological events affecting tumor vasculature. This results in complete tumor ablation and antitumor immunity.

The single arm, non-randomized, open-label, pivotal trial is evaluating padeliporfin VTP among 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 the ureter of the ipsilateral kidney; and with an absence of high-grade cells on cytology.

Additional exclusion criteria include current high-grade or muscle-invasive bladder cancer; current or prior carcinoma in situ in the upper urinary tract; a history of invasive T2 or higher urothelial cancer in the past 2 years; and prior participation in a clinical study involving an investigational agent within 1 month of study entry.

The study includes both an induction and maintenance treatment phase. Patients in both phases will receive intravenous padeliporfin followed by VTP therapy via an outpatient endoscopy.¹ In the induction phase, 1 to 3 treatments with VTP therapy will be administered at either 4-week intervals or until achievement of a CR. Patients who proceed to the maintenance phase will receive SOC treatment alongside VTP therapy every 3months for up to 12 months.

The study’s primary objective is assessment of response rates and durability with padeliporfin VTP at the end of the induction phase. The secondary objective is evaluating the regimen’s safety and tolerability.²

Preliminary efficacy and safety data from ENLIGHTED were previously presented at the 2024 ASCO Annual Meeting. At the data cutoff of January 21, 2024, the CR and PR rates were 77% and 23%, respectively, among 13 evaluable patients who completed their second visit. The most common grade 1/2 treatment-related AEs comprised flank pain (17%), vomiting (8%), fatigue (8%), nausea (6%) and hematuria (6%). Grade 3 SAEs occurred in 9% of patients, and included flank pain, hypertension, renal colic, and urinary tract infections.

Recruitment for the ENLIGHTED study is ongoing.1 A total of 100 are planned for enrollment at 29 sites across the United States, European Union, and Israel. Impact Biotech announced in September 2024 that trial enrollment has exceeded 50%; completion is expected by early 2025. As of the April 29, 2024, data cutoff for the current analysis, 22 patients had begun treatment.

“We are highly encouraged to see consistent patient responses to padeliporfin VTP treatment as we progress the ENLIGHTED Phase 3 study,” Eyal Morag, MD, chief medical officer of ImPact Biotech, concluded. “This expansion of our dataset presented in June further establishes the potential for padeliporfin VTP to transform the treatment landscape for UTUC, by providing efficacy in line with SOC without incurring risk of organ injury or loss. With trial enrollment on track to conclude by early 2025, we look forward to providing subsequent data updates that we expect to provide basis for registration of padeliporfin VTP in low grade UTUC. In parallel, we will look to replicate this effect in other unresectable solid tumors, beginning with our planned phase 1 study in pancreatic ductal adenocarcinoma.”

References

1. 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. November 7, 2024. Accessed November 7, 2024. https://www.biospace.com/press-releases/impact-biotech-presents-updated-interim-phase-3-data-from-enlighted-study-of-padeliporfin-vtp-in-low-grade-utuc-at-emuc-2024
2. Margulis V, Kaufman RP, Marcq G 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). J Clin Oncol. 2024;42(suppl 16):TPS4622. doi:10.1200/JCO.2024.42.16_suppl.TPS4622