NEXT: A phase II, open-label study of nivolumab adjuvant to chemoradiation in patients (pts) with localized muscle invasive bladder cancer.

Abstract

TPS605 Background: In pts with localized muscle invasive bladder cancer (MIBC), trimodality bladder preserving therapy (TMT), with transurethral resection of bladder tumor, radio-sensitizing chemotherapy and definitive radiation, has up to a 50% risk of local and systemic relapse during the 2-year post treatment phase. We hypothesize that by inhibiting immune checkpoints, chemo-radiation induced tumor specific immune response will be enhanced both locally and abscopally, resulting in better failure-free survival (FFS). In the NEXT trial, we evaluate the efficacy of nivolumab after completion of the TMT in this setting. Methods: Pts with localized MIBC who have completed standard TMT are eligible. Pts receive nivolumab 480 mg intravenously every 4 weeks for up to 12 doses. Treatment with nivolumab begins within 90 days of completion of TMT. Subjects undergo surveillance cystoscopic and scan based assessments on study. Archived tumor tissue at baseline and at relapse is obtained for correlative studies. The primary endpoint is 2-year FFS. Secondary endpoints include FFS at 2 years in patients with intact bladder, rate of radical cystectomy (RC), cystoscopic local control, distant FFS in patients with intact bladder and those that undergo RC, overall survival, toxicity and quality of life. Exploratory endpoints include to characterize changes in immune cell subsets that can be correlated with clinical outcome and to assess the correlation of response to PD-L1 expression in pretreatment tumor tissue in the study subjects. The planned sample size for this single arm, open label trial is 28 pts. Kaplan-Meier methods will be used to plot survival endpoints and cystoscopic local control rates. Exact binomial methods will be used to provide 6 months, 1-year and 2-year estimates for these endpoints. The sample size justification is based on the maximum width of a two-sided 95% binomial confidence interval for 2 year FFS. With 28 evaluable subjects, a 95% exact binomial confidence interval, estimated using the method of Clopper-Pearson, will extend no more than 20% from the observed FFS. Clinical trial information: NCT03171025.