AUA 2022: Final Results of a Phase I Trial of WST11 (TOOKAD Soluble) Vascular-Targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma

( The 2022 Annual Meeting of the American Urological Association was host to a podium session about upper tract transitional cell carcinoma. Dr. Wesley Yip presented the final results of a Phase 1 trial of WST11 (TOOKAD Soluble) vascular-targeted photodynamic therapy for the treatment of upper tract urothelial carcinoma.

Dr. Yip highlighted that the standard of care for localized UTUC remains radical nephroureterectomy with up to 80% of patients progressing to CKD3 or ESRD,1 which minimizes adjuvant therapy options and may lead to dialysis. It is estimated that up to 90% of such patients may be overtreated as they have low-grade disease with a minimal metastatic risk.2

Vascular-targeted photodynamic therapy (VTP) is an FDA-approved endoluminal treatment option for urothelial cancers. Padeliporfin (WST-11/TOOKAD Soluble) is a short-acting photodynamic agent. Illumination of tumor tissues with near-infrared light activates VTP, generates reactive oxidative stress, and ablates tissue.

This was a single-institution, non-randomized, open label Phase 1 study that included patients with confirmed UTUC (low or high grade, any size) and residual or recurrent cancer following prior endoscopic treatment. Patients were included if ineligible, unwilling, or refusing surgical resection.

A modified continual reassessment method was conducted to evaluate treatment-related toxicities within 14 days of treatment. The acceptable toxicity threshold rate was set at 20%. 3 dose levels of laser light fluence rate were studied: 100, 150, and 200mW/cm.

The primary endpoint was maximum tolerated dose, and the secondary endpoint was efficacy assessment (complete or partial response).

22 patients were enrolled and 18 formed the final, evaluable cohort.

The baseline patient characteristics are listed below. 74% were low grade. 68% were multifocal. Median tumor diameter was 10 mm.

A complete response was noted in 50% of patients with an additional partial response in 44%. Eight patients underwent a second treatment with a final complete response rate of 68%. The one patient with no response had high grade disease.

Dr. Yip concluded with the following:

  • YTP with WST-11 for UTUC has an acceptable safety profile and promising therapeutic effect
  • MRD of 200 mW/cm was reached
    • Primary endpoint met
  • Safety events were mainly local effects
    • No ureteral strictures, obstructions, or perforations within assessment period
    • Minimal systemic toxicity
    • Complete response in 50% after first treatment, 68% after second treatment
  • Future directions:
    • Phase 3 multicenter ENLIGHTED trial (NCT04620239)
    • Correlative studies ongoing
Presented by: Wesley Yip, MD, SUO Fellow, Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.  


  1. Lane et al. Cancer. 2010;1872(2):188308
  2. Raman et al. Rev Urol.2020;;22(1):1-8.