Despite standard-of-care therapy with transurethral resection of bladder tumor (TURBT) and intravesical BCG instillation, a large percentage of patients with NMIBC have disease recurrence/progression. PD-L1 is widely expressed in urothelial tumors, providing a therapeutic rationale for targeting the PD-1/PD-L1 pathway in NMIBC. KEYNOTE-057 (NCT02625961) is an open-label, phase 2 study designed to evaluate the efficacy of the anti–PD-1 antibody pembrolizumab (pembro) in patients with high-risk, BCG-unresponsive NMIBC.
Eligible patients must be age ≥18 years; have histologically confirmed diagnosis of high-risk, BCG-unresponsive NMIBC (high-grade Ta, T1, and/or carcinoma in situ [CIS] despite adequate BCG treatment); be ineligible for or have declined radical cystectomy; and have ECOG PS 0-2. Patients must have undergone ≥2 cystoscopic procedures with the most recent ≤8 weeks of study start, including complete TURBT (tissue sample must be available). Patients will receive pembro 200 mg Q3W for 24 months or until disease recurrence, progression, or unacceptable toxicity. Patients will be placed into cohorts by presence (cohort A) or absence (cohort B) of CIS based on tissue pathology at screening. Response will be assessed using cystoscopy and urine cytology every 12 weeks for the first 2 years, every 24 weeks for the next 2 years, and every 52 weeks thereafter. CT imaging will be used to assess for metastatic or nodal disease. At 18 months, patients with no evidence of disease may discontinue treatment. Low-grade Ta recurrence will not be considered treatment failure; these patients may undergo repeat TURBT and remain on treatment. AEs will be monitored throughout the study and for 30 days after end of treatment (90 days for serious AEs and events of clinical interest) and graded per CTCAE v4.0. Primary end points are complete response (cohort A) and disease-free survival (cohort B); secondary end points include progression-free survival, overall survival, duration of response, and the relationship between PD-L1 expression and response to treatment. Enrollment will continue until ∼260 patients have enrolled.
Clinical trial identification
Legal entity responsible for the study
Merck & Co., Inc.
Merck & Co., Inc.
T.K. Choueiri: Research funding: Pfizer, Novartis, Merck, Exelixis, Tracon, GSK, BMS, AstraZeneca, Peloton, Roche Consulting/Advisory Role: Pfizer, Bayer, Novartis, Merck, BMS, Roche, Eisai, Prometheus Labs Inc, Foundation Medicine Inc., Cerulean, Peloton, AstraZeneca. K. Nam, R. Perini, S. Keefe: Employee of Merck & Co., Inc. R. Dreicer: Advisory board member: Genentech, Medivation, Exelexis, Ferring Corporate-sponsored research: Genentech, Lilly, Asana. D. Bajorin: Advisory board member: Novartis, Pfizer, Genentech, Urogen, BMS Corporate-sponsored research: Novartis, BMS, Amgen. All other authors have declared no conflicts of interest.