A study of intravesical bacillus Calmette-Guerin (BCG) in combination with ALT-803 in patients with non-muscle invasive bladder cancer.

Abstract

TPS545 Background: The current standard of care for patients with high risk NMIBC is a transurethral resection of the bladder tumor (TURBT) or biopsy followed by a 6-week induction course of intravesical BCG treatment and supplementary maintenance instillations every 3 months thereafter (Lamm 2000). While clinical response is significantly improved with BCG treatment, 50% of patients are still expected to recur within the first 12 months (Sfakianos 2014). Thus, the pursuit of novel agents to prevent progression and recurrence of NMIBC remains critical. This clinical trial evaluates the safety and efficacy of ALT-803, an IL-15 superagonist, plus BCG in BCG-naïve NMIBC patients. Methods: Patients with high-risk NMIBC (any high-grade disease, T1, or CIS) who are BCG naïve, will be randomized and enrolled into one of two study arms to be treated with either ALT-803 plus BCG or BCG alone. Patients will receive treatment via a urinary catheter in the bladder, weekly for 6 consecutive weeks during induction. A response assessment will be performed at Week 12: Patients with no disease or low-grade Ta disease will receive a maintenance course of therapy (3 weekly instillations of either ALT-803 plus BCG or BCG alone). Presence of Ta will require a TURBT procedure. Patients with presence of high-grade Ta, CIS or low-grade T1 disease will receive a re-induction course of therapy (6 weekly instillations of either ALT-803 plus BCG or BCG alone). Presence of Ta/T1 will require a TURBT procedure. Patients with high-grade T1 or greater disease (including disease progression) will be considered a treatment failure. Patients with no disease or low-grade Ta disease at months 6, 12, and 18 are eligible for maintenance treatment according to their assigned randomization. Patients with presence of disease greater than low-grade Ta will be considered a treatment failure. The primary endpoint of the study is the proportion of patients receiving ALT-803 plus BCG who are responders by Month 12 or earlier. Responders are defined as patients who experience a complete response (CIS patients) or no disease recurrence (defined as reappearance of high-risk disease). Enrollment is underway. Clinical trial information: NCT02138734.