A Phase III, randomized, double-blind, multicenter study of adjuvant nivolumab vs placebo in patients (pts) with high-risk invasive urothelial carcinoma (UC; CheckMate 274)

Abstract

Background: Standard of care for muscle‐invasive bladder cancer (predominant form of UC) is cisplatin‐based neoadjuvant chemotherapy followed by radical cystectomy+ pelvic node dissection or cystectomy+ pelvic node dissection alone if cisplatinineligible. Some pts undergo surgical resection followed by adjuvant cisplatin‐based chemotherapy. Many pts are not candidates for adjuvant chemotherapy or are not treated due to lack of proven survival benefit. UC of the ureter or renal pelvis is typically managed with nephroureterectomy. Despite surgery±chemotherapy, pts with invasive UC are at high risk of recurrence and death. Based on the efficacy and safety of the programmed death‐1 (PD‐1) inhibitor nivolumab for metastatic or unresectable UC progressing despite chemotherapy (CheckMate 032 and 275), we are conducting an international phase III study of adjuvant nivolumab vs placebo in pts with invasive UC (originating in bladder, ureter, or renal pelvis) following resection (NCT02632409). Trial design: Pts must have had radical surgical resection±cisplatin‐based neoadjuvant chemotherapy within the past 120 days and be disease‐free (by imaging)≥4 weeks before randomization. Pts who did not receive cisplatin‐based neoadjuvant chemotherapy must be ineligible for or refuse adjuvant cisplatin. Tumor tissue must be provided for biomarker analysis. Pts are ineligible if they had partial cystectomy or partial nephrectomy, or secondary treatment after surgical removal of UC (eg, cisplatin‐based adjuvant chemotherapy), prior malignancy within 3 years except those treated with curative intent and in remission, or any condition requiring systemic treatment with immunosuppressants (eg, corticosteroids) within 2 weeks of treatment. Recruitment began in February 2016; target enrollment is ∼640 pts. Co‐primary endpoints: Disease‐free survival (defined as the time between date of randomization and date of first recurrence or death) in pts with tumors expressing≥1% PD‐ligand 1 and in all randomized pts. Secondary endpoints: Non‐urothelial tract recurrence‐free survival, disease‐specific survival, overall survival.