TLD-1433 photodynamic therapy for BCG-unresponsive NMIBC: a Phase IB clinical study (Conference Presentation)

Abstract

For patients failing standard Bacillus Calmette-Guerin based immunotherapy for Non-Muscle Invasive Bladder Cancer (NMIBC), PDT may delay or prevent cystectomy. A Phase IB clinical trial evaluated the feasibility and safety of TLD1433, a novel Ruthenium coordination-complex as photosensitizer (PS) for PDT. The clinical trial combined PS instillation for one hour and the use of strongly attenuated green (525nm) light to reduce PDT caused damage to the bladder wall. The low and high PS doses were defined as 0.35mg and 0.7mg TLD1433 per cm^2 bladder surface (N=3 each) and 90+/-9J/cm^2 as target radiant exposure on the bladder wall. The PS concentration in the urine and blood at 24hrs post instillation was below 1ng/ml indicating rapid drug clearing. In all patients, the average target radiant exposure was attained as verified by irradiance sensors in the bladder. The average measured irradiance was ~ 15mW/cm^2, never exceeding 35mW/cm2 at the sensor positions. At 30 days post-treatment, all patients receiving the low PS dose tolerated the procedure well with no grade 3, 4 or 5 AEs. Three patients were then treated at the Therapeutic Dose, again with no grade 3, 4 or 5 AEs, and an identical pharmacokinetic profile to the half dose. At half dose, all patients had recurrent, but no progressive NMIBC noted at the 180-day cystoscopy. At therapeutic dose, 2 of 3 patients were tumour-free at the 180-day cystoscopy. Moderate bladder irritability was reported at full dose which primarily resolved within 90 days.