ImPact Biotech announced promising interim efficacy and safety data from its pivotal Phase 3 ENLIGHTED trial evaluating Padeliporfin vascular targeted photodynamic (VTP) therapy in patients with low-grade upper tract urothelial cancer (UTUC). The results, presented at the American Society of Clinical Oncology 2024 Annual Meeting, showed a 77% complete response rate in evaluable patients who completed the induction treatment phase.
Strong Efficacy Signal in Difficult-to-Treat Cancer
Of the 13 response-evaluable patients who completed the Induction Treatment Phase (ITP), 10 patients (77%) achieved a complete response. The data represents patients treated as of January 21, 2024, with 17 patients having begun treatment in the ongoing study.
"These results emphasize the potential of Padeliporfin VTP as a viable treatment option for patients with low-grade UTUC," said Vitaly Margulis, M.D., Professor of Urology at UT Southwestern Medical Center. "UTUC is difficult to treat, as it is not easily resectable without inflicting organ damage and current standards of care commonly require onerous treatment regimens that do not match surgery in efficacy."
Favorable Safety Profile Maintained
The treatment demonstrated a well-tolerated safety profile consistent with previous Phase 1 study data and preliminary Phase 3 results. Adverse events were primarily Grade 1 or 2, mostly gastrointestinal-related, with Grade 3 events observed in only 9% of patients. All adverse events resolved within two to seven days, and no Grade 4 or 5 serious adverse events were observed.
Novel Treatment Approach
The Phase 3 ENLIGHTED study is a single-arm, non-randomized, open-label pivotal trial conducted across 29 clinical sites globally, targeting enrollment of up to 100 patients with new or recurrent low-grade, non-invasive UTUC of the kidney or ureter. The study consists of two phases: an Induction Treatment Phase and Maintenance Treatment Phase.
During treatment, Padeliporfin, a photosensitizing drug, is administered intravenously followed by VTP therapy performed via outpatient endoscopy. The procedure applies laser fiber illumination for 10 minutes in proximity to the tumor, leading to local activation of Padeliporfin in the tumor microenvironment. The ITP consists of one to three treatments with VTP therapy at four-week intervals or until complete response is achieved, followed by the MTP with standard-of-care treatment alongside VTP therapy administered every three months for up to 12 months.
Clinical Development Timeline
ImPact continues recruiting for the ENLIGHTED study and expects to complete enrollment by the end of 2024. The company anticipates presenting an interim analysis in the second half of 2024. The study's primary objective is to assess response rate to Padeliporfin VTP treatment at the end of ITP, with secondary objectives evaluating safety, tolerability, and duration of response.
"This dataset underscores our conviction that Padeliporfin VTP may provide immense clinical benefit as an alternative that delivers efficacy more in line with surgical intervention than standard-of-care therapeutics but without the associated risk of organ injury or loss," said Eyal Morag, M.D., Chief Medical Officer of ImPact Biotech.
Expanding Pipeline Applications
Beyond UTUC, ImPact plans to evaluate Padeliporfin VTP in other solid tumors, including pancreatic ductal adenocarcinoma (PDAC), high-grade UTUC, and non-small cell lung cancer (NSCLC). At ASCO, the company also presented a trials-in-progress poster featuring the design of its Phase 1 study in PDAC, which is expected to initiate patient dosing in the coming weeks. The two-part, dose-escalation and expansion study will evaluate safety and tolerability in Part A, and preliminary efficacy in Part B, with responses defined by conversion from unresectable to resectable disease.
