(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31 and June 4 was host to the Poster Session: Genitourinary Cancer: Kidney and Bladder. Dr. Genia Alpert presented the trial in progress ENLIGHTED: a phase 3 study assessing the efficacy and safety of padeliporfin, a vascular targeted photodynamic therapy (VTP) for treatment of low-grade upper tract urothelial cancer (LG UTUC). Clinical trial identifier: NCT04620239.
Padeliporfin vascular targeted photodynamic therapy (VTP) is a combination product, whereby the drug, padeliporfin (a photosensitizer), is intravenously administered, a device: a laser light delivery system, emits near-infrared (NIR) light at 753 nm, and an optic fiber delivers the light to the target lesion(s) in the upper tract urothelium.
Upon laser light activation, Padeliporfin triggers a cascade of events (non-thermal radical oxygen species (ROS) generation, vascular occlusion, necrosis) that strongly impact tumor vasculature and induce an anti-tumor immune response, as illustrated below:
In the Phase 1 study evaluating padeliporfin, VTP (NCT03617003), 19 patients received up to two endoscopic VTP treatments with 6 months of follow-up. The response rate at 30 days was 94% (50% complete response, 44% partial response). Eight patients received a second VTP treatment, resulting in a final observed complete response (CR) rate of 68%. All patients were able to spare their kidneys at the 6-month follow-up mark.
Dr. Alpert presented at ASCO this year the ENdoluminal LIGHT activated treatment of upper tract urothelial carcinoma (ENLIGHTED) trial: a single-arm, open-label, global pivotal phase 3 trial being conducted across 29 sites in the United States, Europe, and Israel. The target sample size is 100 patient enrollees, with 75 potentially evaluable.
The ENLIGHTED study hypothesized that Padeliporfin VTP treatment would effectively ablate low-grade upper tract urothelial carcinoma lesions, supporting the clinical goal of kidney preservation. This trial is divided into two phases: the induction and maintenance Treatment Phases (ITP and MTP). The ITP consists of 1-3 VTPs every 28 days. If complete response (CR) is not achieved after the first VTP, up to two additional VTPs are allowed. If CR is achieved in the ITP, patients are allowed to enter the MTP (12 months). In the MTP, VTPs can be provided every 3 months for patients with recurrent tumor that is deemed treatable (see definition in the inclusion criteria below). A long-term follow-up phase is planned for patients completing the MTP. These patients will be followed for safety for 48 months with no VTPs.
This study included patients with new or recurrent low-grade, non-invasive upper tract urothelial carcinoma, meeting the following criteria:
- Male and female patients 18 years or older
- Up to two biopsy-proven low-grade UTUC tumors with the largest index tumor 5-15 mm in diameter (as measured by endoscopy), located in the calyces, renal pelvis, or in the ureter of the ipsilateral kidney
- Absence of high-grade cancer cells on cytology.
- Ureter involvement can be in one ureteral location (≤ 20 mm of contiguous ureteral length)
Key exclusion criteria included:
- Current high-grade or muscle-invasive (>pT1) urothelial carcinoma of the bladder
- Carcinoma in situ (CIS) – current or previous in the upper urinary tract
- History of invasive T2 or higher urothelial cancer in the preceding two years
- Prohibited medication that could not be adjusted or discontinued prior to study treatment
- Patients with photosensitive skin diseases or porphyria
The primary objective of this trial was to demonstrate the efficacy and durability of Padeliporfin VTP and the secondary objectives included evaluating Padeliporfin VTP-related safety and tolerability in treating low-grade UTUC tumors in the kidney and ureter.
The study schema is illustrated below. Patients underwent initial screening to confirm eligibility. They subsequently underwent induction treatment at 1–3 months thereafter. They received 1–3 padeliporfin VTP treatments under anesthesia about four weeks apart. If a complete response (defined as no visible tumor endoscopically, negative biopsy/cytology) was not achieved after three treatments on Visit 2 (or if the disease had progressed), patients were discontinued from the Treatment Phases and entered the long-term follow-up phase.
The cut-off date for data analysis was January 2024. At that point, 17 patients had been treated, and 13 had completed visit 2. As outlined in the table below, the mean age was 67 years, the most frequent tumor location was the kidney (76%), and most patients (59%) had a single tumor.
Of the treated patients, 10 (77%) achieved a complete response, and three (23%) achieved a partial response.
With regard to treatment-related adverse events, the majority were grade 1–2 in severity, with grade 3 serious adverse events observed in 9% of patients (flank pain, hypertension, renal colic, and urinary tract infections). All adverse events resolved within 2-7 days after treatment. No grade 4–5 adverse events were observed up to the time of data cut-off.
Based on these preliminary results, Dr. Alpert concluded that:
- Padeliporfin VTP demonstrates early evidence of safety and efficacy with preliminary data consistent with prior experience (Phase I study)
- The phase 3 ENLIGHTED trial is actively recruiting patients and its primary objective is to show that Padeliporfin VTP treatment would effectively ablate LG UTUC tumors.
- Long-term results are expected to provide the basis for treatment approval
Presented by: Genia Alpert, MD, PhD, Medical Director, Medical Monitor, Impact (Steba) Biotech, Luxembourg
Written by: Julian Chavarriaga, MD – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31st and June 4th.
Related content: ENLIGHTED Trial: New Promising Approach for Low-Grade Upper Tract Urothelial Carcinoma - Vitaly Margulis
References: