Breakthrough Clinical Results
ImPact Biotech announced that it will present interim data from its Phase 3 ENLIGHTED study of Padeliporfin VTP in patients with low-grade upper tract urothelial cancer (UTUC) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The interim analysis includes data from 50% of the targeted evaluable patient enrollment. The ENLIGHTED study is a single-arm, non-randomized, open-label trial evaluating Padeliporfin VTP, a vascular targeted photodynamic therapy, across 29 clinical sites globally. The primary objective is to assess the response rate at the end of the Induction Treatment Phase, with secondary objectives focusing on safety, tolerability, and duration of response. The company believes this interim analysis will support the value proposition of Padeliporfin VTP as a best-in-class treatment option for UTUC.
Key Highlights
- Interim analysis of the Phase 3 ENLIGHTED study of Padeliporfin VTP in low-grade UTUC to be presented at ASCO 2025.
- Data from 50% of the targeted evaluable patient enrollment will be included in the presentation.
- The ENLIGHTED study is evaluating Padeliporfin VTP as a potential best-in-class treatment for UTUC.
- The study's primary objective is to assess the response rate to Padeliporfin VTP treatment.
Study Design Parameters
Key Trials for Upper Tract Urothelial Cancer: Study Design Parameters and Endpoints
POUT Trial
- Retrospective analysis of 240 UTUC patients at Johns Hopkins Hospital from 2003-2017
- Patients with biopsy proven high grade disease and visible lesion on cross-sectional imaging were offered neoadjuvant chemotherapy before radical nephroureterectomy
- Time-matched control group with biopsy proven high grade disease underwent surgery alone
- Endpoints: pathological stage distribution, complete remission rate
- Results showed 46.5% reduction in pT3+ disease in neoadjuvant chemotherapy group, 9.4% complete remission rate
SAUL Study (Atezolizumab)
- Single-arm study of 1,004 patients with metastatic urinary tract carcinoma
- Intervention: atezolizumab 1,200 mg every 3 weeks until disease progression/toxicity/loss of benefit
- Primary endpoint: safety
- Secondary endpoint: efficacy
- Prespecified analyses by PD-L1 status, age, ECOG PS, renal impairment
- Post hoc analyses of outcomes by tumor location
- Included understudied populations (elderly, renal impairment, ECOG PS 2, upper tract tumors)
Taiwan UTUC Collaboration Study
- Retrospective study of variant UTUC following radical nephroureterectomy
- 245 patients with variant UTUC identified from database of 3,109 UTUC patients
- Compared patients who received adjuvant chemotherapy versus those who didn't
- Used propensity score matching to reduce treatment assignment bias
- Endpoints: overall survival, cancer-specific survival, and disease-free survival
- Multivariate Cox regression model used for survival analysis
Ureteroscopy Follow-Up Study
- Single-center cohort of 71 patients with nonmetastatic UTUC treated with ureteroscopy (2010-2020)
- Follow-up protocol: endoscopy at 3-month intervals (first year), 6-month intervals (years 2-3), yearly thereafter
- Outcomes measured: ipsilateral UTUC recurrence, treatment conversion, tumor upgrading
- Statistical analysis: Andersen-Gill model for recurrent events, multivariable Cox regression
- Median follow-up: 49.5 months
Multi-institutional Retrospective Analysis
- Analysis of patients with high-risk UTUC who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021
- 84 patients with UTUC received neo-adjuvant chemotherapy
- 52.4% (44) received cisplatin-based chemotherapy, and 26.2% (22) had a carboplatin-based regimen
- Logistic regression analyses investigated clinical parameters for response after neoadjuvant chemotherapy
- Cox proportional hazard models assessed effect of response on oncological outcomes
NCDB Analysis
- Involved 1,658 patients with cN+M0 UTUC identified from the National Cancer Database
- Patients stratified into treatment groups
- Survival analysis completed using a multivariate Cox regression model
Systematic Review and Meta-analysis
- Review of six prospective trials with 2,537 patients, including 396 (15.6%) with advanced UTUC
Neoadjuvant Chemotherapy Evaluation
- Evaluated efficacy of neoadjuvant chemotherapy with gemcitabine and cisplatin (NAC-GC) in patients with cT3N0M0 UTUC who underwent radical nephroureterectomy (1999-2021)
- 44 patients: 20 (45.5%) in the NAC-GC group and 24 (54.5%) in the non-NAC-GC group
- Oncological prognosis assessed using progression-free survival and overall survival
Randomized Controlled Trial
- Primary endpoint: patient recruitment rate
- Secondary endpoints: oncological outcomes including recurrence-free survival and progression-free survival
- Patient compliance rate for the study protocol was 93.3%
Incidence and Prevalence
Global Incidence and Prevalence of Upper Tract Urothelial Cancer
Upper tract urothelial carcinoma (UTUC) represents a rare subset of urothelial cancers with a poor prognosis. According to recent data, UTUC accounts for 5-10% of all urothelial cancers and 10% of renal tumors.
Incidence Data
In 2014, approximately 15,000 new cases were diagnosed in the United States. UTUC demonstrates a clear gender disparity, being more common in men than women, with a male-to-female ratio of 2:1.
Detailed epidemiological data from Norway provides insight into recent trends. Between 1999-2018, the overall age-standardized incidence rate was 3.88 per 100,000 population. The Norwegian data revealed that UTUC incidence increased from 3.21 to 4.70 per 100,000 from the first to last 5-year periods of the study.
In Norway, UTUC constituted 11.8% of all urothelial cancers, with this proportion increasing from 9.9% to 12.8% over the study period. This increasing trend affected all age groups except those under 60 years of age and was observed regardless of gender or anatomical location.
The mean patient age at diagnosis also increased from 71.5 to 73.4 years during the Norwegian study period.
Disease Characteristics and Risk Factors
At initial diagnosis, approximately 60% of UTUC tumors are already invasive, contributing to the poor prognosis associated with this malignancy.
Several risk factors have been identified for UTUC development: - Cigarette smoking - Occupational exposure - Balkan endemic nephropathy - Chinese herb nephropathy - Aristolochic acid exposure
Genetic Factors
There is a significant genetic component to some UTUC cases. Up to 21% of new UTUC cases may have unrecognized Lynch Syndrome as the underlying cause. This genetic condition, also known as hereditary nonpolyposis colorectal carcinoma (HNPCC), is linked to the development of UTUC.
Drug used in other indications
Based on the provided context, there is no information available about Padeliporfin VTP (TOOKAD) being trialed for indications other than Upper tract urothelial cancer (UTUC). The context contains conflicting information where one part mentions that Padeliporfin VTP therapy is "currently being studied" for UTUC patients, while another part indicates that none of the input strings mention "Padeliporfin" or "VTP" or any trials related to this treatment.
The only intervention model mentioned in the context is a dose escalation model with "increasing light fluence (100-200 mW/cm) using a modified continual reassessment method" for a Phase I trial of UTUC.
The context also references: - A Phase I trial (NCT03617003) - The Phase 3 ENLIGHTED trial (NCT04620239) for upper tract urothelial carcinoma
No other indications or intervention models for Padeliporfin VTP trials are described in the provided context.