AUA 2023: An Interim Analysis of a Phase II Clinical Study of Intravesical Photo Dynamic Therapy in Patients With BCG-Unresponsive Non-muscle Invasive Bladder Cancer (NMIBC) Carcinoma in-situ (CIS)

( Dr. Girish Kulkarni presents an interim analysis of a phase II clinical trial of intravesical PDT in BCG-unresponsive NMIBC CIS, with or without papillary disease. As he notes, and many of us understand, novel therapies are required for BCG-unresponsive, high risk non-muscle invasive bladder cancer. Patients are looking for bladder sparing options. One potential option is intravesical Photo Dynamic Therapy (PDT). Herein, they report the interim results of a Phase II Clinical Study of PDT in patients with BCG-unresponsive carcinoma in situ (CIS) (+/- papillary disease).

Of the planned 125 patients, 57 patients have been treated with two study treatments (Day 0 and Day 180) consisting of an intravesical instillation of the photosensitizer (TLD-1433 (0.70 mg/cm2)) followed by activation with a 520 nm intravesical laser under general anesthesia (Study Device TLC-3200) to a total of 90 J/cm2 of laser light. They also included 3 patients treated in a preceding Phase Ib NMIBC clinical study assessing the safety of TLD-1433 PDT, who were treated at the same parameters, for a total of 44 patients.

The primary outcome was complete response (CR) at any point in time.

The secondary outcome was duration of CR, after initial CR.

  • Patients with a negative cystoscopy and positive cytology were defined as indeterminate response (IR), as these patients remain under investigation for lower and upper tract urothelial carcinoma.

A tertiary objective was safety, evaluated by the incidence and severity of grade 4 adverse events (AEs) that did not resolve within 450 days post treatment. All AEs were tracked for resolution to 450 days.

Interim analysis includes 52 patients at the 90 day mark and 12 patients at the 450 day mark. ]

70% of patients had CIS alone, 10% had CIS + Ta, and remainder had CIS + T1 disease.

Most patients were heavily pre-treated with BCG. 21% had > 19 treatments in the past.

For evaluable patients, a primary outcome of 54% CR at any point in time was achieved. Of the 12 patients who were evaluated at 450 days, 8 had CR (67%).

There have been nine serious adverse events (SAE) identified (1 grade 1 (sepsis), 2 grade II (tachycardia, hematuria), 3 grade III (acute kidney injury, cellulitis), 2 grade IV (urosepsis, depression/anxiety) and 1 grade V (cardiac arrest)). None of the SAEs were deemed to be directly related to PDT, per the Data Safety Monitoring Board.

This interim data supports that PDT provides a viable treatment option for patients with BCG unresponsive CIS (+/- papillary disease) with an acceptable safety profile.

Presented by: Girish Kulkarni, MD, PHD, FRCSC, University of Toronto

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023 

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