A multicenter clinical trial of intravesical BCG in combination with ALT-803 in patients with BCG-unresponsive non-muscle invasive bladder cancer.

Abstract

TPS544 Background: BCG unresponsive NMIBC includes patients with persistent high-grade disease or recurrence within 6 months of receiving at least two courses of BCG; or T1 high-grade disease at the first evaluation following BCG induction alone. The recommendation after failing BCG in patients suitable for surgery is cystectomy or for unwilling/unfit patients, salvage chemotherapy or immunotherapy (administered with limited success). This highlights a critical need for novel preservation therapies to facilitate a better quality of life and reduce health-care costs for patients who are unresponsive to BCG (Correa 2015, Dalbagni 2006, Dinney 2013, Kamat 2017). Altor BioScience has initiated a phase II clinical study in BCG unresponsive patients to expand on promising data collected from a compassionate use patient who remains disease free more than 2.5 years after ALT-803 plus BCG treatment for refractory NMIBC (Huang 2017). Methods: This is a Phase II, open-label, single-arm, multicenter study of intravesical BCG plus ALT-803 in patients with BCG unresponsive high grade NMIBC. Group A will enroll patients who have histologically confirmed presence of CIS [with or without Ta or T1 disease]. Group B will enroll patients who have histologically confirmed high-grade Ta or T1 disease (in the absence of CIS). All patients will receive BCG plus ALT-803 weekly for 6 consecutive weeks. A cystoscopy will be performed at Week 12. Patients with no disease or low-grade Ta will receive a maintenance course of therapy (3 weekly instillations of BCG plus ALT-803). Patients with residual CIS and/or high-grade Ta will receive a re-induction course of therapy. Presence of Ta will require a TURBT. Patients with greater than or equal to T1 disease or new CIS will be deemed treatment failures. Patients with a Complete Response (CR) or low-risk disease at Months 6, 9 and 12 are eligible for continued BCG plus ALT-803 maintenance. Patients will be followed for recurrence, progression, and survival. The primary endpoint is to assess complete response (CR; absence of lesions on cystoscopy or negative, for cause, biopsies along with negative urine cytology) of CIS at six months. Enrollment is underway. Clinical trial information: NCT03022825.