MP63-01: 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)
Introduction: Novel therapies are required for BCG-unresponsive, high risk non-muscle invasive bladder cancer. We report the interim results of a Phase II Clinical Study of intravesical Photo Dynamic Therapy (PDT) in patients with BCG-unresponsive carcinoma in-situ (CIS) (+/- papillary disease). Methods: 41 of planned 125 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. We have 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. 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. 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. Results: Primary and secondary outcomes for the first 41 patients plus the 3 Phase Ib patients (n=44) are listed in the table. For evaluable patients, a primary outcome of 55.3% CR at any point in time was achieved, with a secondary outcome of duration of response of 21% CR at 450 days. 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 (cardiac arrest)). None of the SAEs were deemed to be directly related to PDT, per the Data Safety Monitoring Board. Conclusions: The interim data supports that PDT provides a viable treatment option for patients with BCG unresponsive CIS (+/- papillary disease) with an acceptable safety profile. SOURCE OF Funding: Theralase Technologies Inc.
