ImPact Biotech has announced that its Phase 3 ENLIGHTED trial, evaluating Padeliporfin vascular targeted photodynamic (VTP) therapy for patients with low-grade upper tract urothelial carcinoma (UTUC), has reached the 50% patient enrollment mark. This milestone brings the company closer to potentially offering a new treatment option for this challenging cancer.
The ENLIGHTED trial (NCT04620239) is a single-arm, non-randomized, open-label study aiming to enroll 100 adult patients across 29 sites in the United States, European Union, and Israel. The study consists of two phases: an Induction Treatment Phase (ITP) and a Maintenance Treatment Phase (MTP).
Padeliporfin, a photosensitizing drug, is administered intravenously, followed by VTP therapy. This involves an outpatient endoscopy where a laser fiber illuminates the tumor for 10 minutes, locally activating Padeliporfin within the tumor microenvironment.
Interim Results and Future Expectations
Interim data presented at the American Society of Clinical Oncology (ASCO) 2024 meeting in June showed promising results. Among the first 17 patients enrolled, 13 completed the induction phase, with 10 of those patients (77%) achieving a complete response. The company anticipates sharing further interim data in the fourth quarter of this year and expects to complete enrollment by the first quarter of 2025.
According to Eyal Morag, M.D., Chief Medical Officer of ImPact Biotech, the company is well-positioned to advance the development of Padeliporfin VTP as a potential best-in-class treatment for low-grade UTUC, citing the progress in patient recruitment, positive preliminary results, and a substantial investment commitment from the European Innovation Council (EIC).
Safety and Tolerability
The interim data also provided insights into the safety profile of Padeliporfin VTP. The most common grade 1-2 adverse events (AEs) included flank pain (17%), vomiting (8%), fatigue (8%), nausea (6%), and hematuria (6%). Grade 3 serious AEs (9%) consisted of flank pain, hypertension, renal colic, and urinary tract infection. All AEs resolved within 2 to 7 days, and no grade 4-5 AEs were reported.
Trial Design and Objectives
The ENLIGHTED trial's primary objective is to assess the efficacy and durability of Padeliporfin VTP therapy. Secondary objectives include evaluating the treatment's safety and tolerability. Patients enrolled in the trial have recurrent low-grade, non-invasive UTUC with up to two biopsy-proven tumor lesions of low-grade involvement.
During the induction phase, patients receive one to three VTP treatments every four weeks until a complete response is achieved or treatment failure is determined. Complete response is defined as the absence of visual tumor on endoscopy, no evidence of tumor on biopsy, and negative urine cytology.
Patients who achieve a complete response progress to the maintenance phase, where they undergo endoscopic evaluation every three months. Recurrent tumors within the first 12 months are treated with VTP. Following the maintenance phase, patients are followed for an additional 48 months to assess long-term outcomes.
