A phase 2/3 multicenter trial evaluating safety and efficacy of a new mucoadhesive gemcitabine suspension for ablation of upper tract urothelial carcinoma.

TPS889 Background: Patients with large, multifocal, or frequently recurrent low-grade (LG) upper tract urothelial carcinoma (UTUC) often require nephroureterectomy to effectively manage their disease, despite the low oncologic risk of progression. There is a need for safer, more effective nephron-sparing treatments. Intraluminal therapies are underdeveloped and limited by the short dwell time of drugs in the collecting system. Intravesical gemcitabine has shown efficacy and minimal toxicity in treating bladder urothelial carcinoma, suggesting a similar potential for UTUC. The investigational drug (ST-02) is a novel mucoadhesive gemcitabine suspension designed for pyelocaliceal instillation. It changes from a liquid to a mucoadhesive gel in the collecting system once in contact with water, thereby facilitating prolonged exposure to gemcitabine. This trial aims to demonstrate that intraluminal administration of ST-02 can effectively and safely ablate LG UTUC. Methods: This is a prospective, multicenter, single-arm, open-label phase II/III clinical trial (NCT06124976) designed to enroll 70 patients with biopsy-confirmed LG UTUC. The study employs a two-stage design with early stopping rules, where the trial will be halted if there are 8 or fewer complete responses (CR) among the first 30 participants (phase II). Eligible patients must have tumors measuring 5-15 mm at treatment initiation. ST-02 will be instilled via retrograde or antegrade catheterization weekly for 6 weeks. The primary endpoint is the CR rate, assessed by ureteroscopic evaluation 6 weeks after the last instillation. Maintenance therapy with ST-02 will be offered to participants with ongoing CR at 3, 6, 9, 12, and 15 months. Secondary objectives include evaluating the durability of CR at 12 months, objective response rates based on tumor size, event-free survival, and safety. The trial includes a safety lead-in phase with pharmacokinetic evaluation in the first 10 patients. An independent Data Monitoring Committee will oversee safety and efficacy assessments. Clinical trial information: NCT06124976 .