ASCO GU 2023: A Phase II Clinical Study of Intravesical Photo Dynamic Therapy in Patients with BCG-Unresponsive NMIBC (Interim Analysis)

(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on urothelial cancer, the Poster Session B: Prostate Cancer and Urothelial Carcinoma included a presentation from Dr. Girish Kulkarni highlighting interim results assessing of intravesical photo dynamic therapy in patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).

There is a significant clinical need for novel treatment approaches in patients with BCG-unresponsive, high risk non-muscle invasive bladder cancer. In this abstract, the authors report interim results of a Phase II Clinical Study of Intravesical Photo Dynamic Therapy (PDT) in patients with BCG-Unresponsive Carcinoma In-Situ (CIS) with or without papillary disease.

In this trial with a target planned sample size of 125 patients, 42 patients have been enrolled and 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 (NCT03945162). The primary study outcome assessed was an efficacy endpoint of Complete Response (CR), at any point in time. The secondary outcome was duration of CR at 12 months following an initial CR. Finally, the authors assessed safety as a tertiary endpoint, evaluated by the incidence and severity of Adverse Events, Grade 4 or higher that do not resolve within 450 days post treatment. Patients with a negative cystoscopy and positive cytology were defined as having an indeterminate response (IR), as these patients remain under investigation for lower and upper tract urothelial carcinoma.

As of this interim analysis, the authors evaluated the first 42 patients, along with 3 patients treated in a preceding Phase Ib NMIBC clinical study assessing the safety of TLD-1433 PDT, treated using the same parameters, for a total of 45 patients.

The interim clinical data demonstrates a 90 day CR of 53% and a duration of response at 360 and 450 days of 29% and 28%, respectively.

Response table.jpg

At this interim evaluation, there have been eight Serious Adverse Events (SAE) identified 2 Grade II (tachycardia, hematuria), 3 Grade III (acute kidney injury, cellulitis), 2 Grade IV (urosepsis, depression/anxiety) and 1 Grade V]. None of the SAEs were deemed to be directly related to the study treatment.

Thus, the authors concluded that these interim data support Photo Dynamic Therapy as a viable treatment option for patients with BCG unresponsive CIS (+/- papillary disease) with an acceptable safety profile.

Presented by: Girish S. Kulkarni, MD, PhD | Division of Urology, Princess Margaret Cancer Center, University Health Network, University of Toronto