Phase 3 trial progresses of padeliporfin VTP therapy in upper tract urothelial carcinoma

The 50% patient enrollment threshold has been reached in the phase 3 ENLIGHTED trial (NCT04620239), exploring padeliporfin vascular targeted photodynamic (VTP) therapy in patients with low-grade upper tract urothelial carcinoma (UTUC), ImPact Biotech announced in a news release.¹

Interim data showed that 77% of patients achieved a complete response.

“We are pleased to have enrolled over 50% of the patients in our phase 3 ENLIGHTED study, marking an important milestone for ImPact Biotech,” said Eyal Morag, MD, Chief Medical Officer of ImPact Biotech, in the news release.¹ “With this recent progress and continued momentum in patient recruitment, we anticipate reaching complete enrollment by the first quarter of 2025. Based on the positive preliminary results and encouraging advances in the study, as well as a substantial investment commitment from the European Innovation Council (EIC), we are well-positioned to forge ahead with the development of padeliporfin VTP as a potential best-in-class and differentiated novel treatment in low-grade UTUC.”

In total, the single-arm, non-randomized, open-label ENLIGHTED trial plans to enroll 100 adult patients with low-grade UTUC across 29 clinical trial sites in the United States, European Union, and Israel.² Interim results from the trial were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in June. Additional data from the trial is expected to be reported in Q4 of 2024, with completed enrollment anticipated for Q1 of 2025.

For the trial, “Padeliporfin, a photosensitizing drug, is administered intravenously, and VTP therapy is performed via an outpatient endoscopy, which applies a laser fiber illumination for 10 minutes in the proximity of the tumor, leading to local activation of padeliporfin in the tumor,” according to the company.¹

Data presented at ASCO included the first 17 patients enrolled in the trial, with 13 patients having completed visit 2 in the study (following the induction phase).³ Of those, 10 patients (77%) achieved a complete response, and 3 patients (23%) achieved a partial response.

The most common grade 1-2 adverse events (AEs) included flank pain (17%), vomiting (8%), fatigue (8%), nausea (6%), and hematuria (6%). The most common grade 3 serious AEs (9%) were flank pain, hypertension, renal colic, and urinary tract infection. All AEs were resolved within 2 to 7 days, and there were no instances of grade 4-5 AEs.

In 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.

To be eligible for enrollment in the trial, patients need to have recurrent low-grade, non-invasive UTUC and up to 2 biopsy-proven tumor lesions of low-grade involvement. The primary objective is to assess the efficacy and durability of effect of padeliporfin VTP therapy. The secondary objective is to assess safety and tolerability of treatment.

Overall, the authors concluded, “To date, padeliporfin VTP has shown evidence of safety and efficacy with preliminary data that is consistent with prior experience. Recruitment for the ENLIGHTED trial is ongoing, with results expected to provide basis for approval of a new therapy that clinically benefits [patients].”³

References

1. ImPact Biotech announces 50% enrollment in phase 3 ENLIGHTED clinical trial of padeliporfin VTP in low grade upper tract urothelial cancer. News release. ImPact Biotech. September 27, 2024. Accessed September 30, 2024. https://www.globenewswire.com/en/news-release/2024/09/27/2954460/0/en/ImPact-Biotech-Announces-50-Enrollment-in-Phase-3-ENLIGHTED-Clinical-Trial-of-Padeliporfin-VTP-in-Low-Grade-Upper-Tract-Urothelial-Cancer.html

2. ENdoluminal LIGHT ActivatED treatment of upper tract urothelial cancer (ENLIGHTED) study (UCM301). ClinicalTrials.gov. Last updated March 18, 2024. Accessed September 30, 2024. https://clinicaltrials.gov/study/NCT04620239

3. 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). doi: 10.1200/JCO.2024.42.16_suppl.TPS4622