SUO 2018: TLD-1433 Photodynamic Therapy for BCG-Unresponsive NMIBC - A Phase IB Clinical Study
In this presented study, the authors aimed to assess the safety, tolerability, pharmacokinetics and exploratory efficacy of TLD-1433 Photodynamic Therapy in patients with non-muscle invasive bladder cancer which is BCG-Unresponsive.
This study involved intravesical instillation of TLD-1433 in the preoperative holding area for 1-hour prior surgery. TLD-1433 was activated transurethrally with a rigid cystoscope under general anesthesia with 525 nm, 3 W laser using a target dose of 90 J/cm2 of bladder surface area. The laser system measured irradiance [mw/cm2] throughout the case, enabling optimization of the laser light as a function of bladder size, shape, and diffuse reflectance. A 3+3 dose escalation strategy was utilized, starting with the Maximum Recommended Starting Dose (MRSD) of 0.35 mg/cm2 with an increase to the planned Therapeutic Dose (TD) of 0.70 mg/cm2. In all cases, the safety, tolerability, and pharmacokinetics (using blood and urine samples) was performed. These were reviewed by an independent Data Safety and Monitoring Board. Adverse events were measured using the World Health Organization classification. Lastly, patients underwent cystoscopy at 3 and 6 following treatment to assess efficacy, which was defined as recurrence-free survival.
At the beginning, three patients were treated at the MRSD of 0.35 mg/kg2. At 30 days following the procedure, all patients had tolerated it well with no grade 3-5 adverse events. Pharmacokinetic analysis demonstrated minimal systemic absorption of the drug without any photosensitivity reactions. The drug was cleared from the plasma within 72 hours of activation.
Next, three patients were then treated at the therapeutic dose, experiencing no grade 3-5 adverse events and an identical pharmacokinetic profile to that seen when half the dose was used. Six months following the procedure with half the dose, all patients manifested recurrently, but non-progressive non-muscle invasive bladder cancer. In contrast, when the therapeutic dose was used, 2 of the 3 patients were tumor-free six months following the procedure. When full dose was used, moderate bladder irritability was reported, but within 90 days it had resolved.
Summarizing this study, the authors concluded that TLD-1433 photodynamic therapy is a safe and well-tolerated treatment when the therapeutic dose was used. Lasting complete response at six months following the procedure suggests that this treatment could be a relevant therapeutic option for non-muscle invasive bladder tumor which is BCG-Unresponsive. These promising results warrant further investigation in a phase II trial.
Presented by: Girish S. Kulkarni, MD, Ph.D., FRCSC, Medical Advisory and Research Board, The University of Toronto, UHN, Princess Margaret Cancer Center, Toronto, Ontario, Canada
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona