NEXT: A single-arm, phase 2, open-label study of adjuvant nivolumab after completion of chemo-radiation therapy in patients with localized muscle-invasive bladder cancer.

Abstract

506 Background: Nivolumab has known efficacy as adjuvant therapy after radical cystectomy in localized muscle invasive bladder cancer (MIBC). We are evaluating the efficacy of nivolumab adjuvant to definitive chemo-radiation therapy (CRT) in MIBC. Methods: In the NEXT study, we are currently enrolling patients with localized MIBC undergoing standard CRT. Participants are started on nivolumab 480 mg IV every 4 weeks (up to 12 doses) within 90 days of completion of CRT. Cystoscopic and scan-based assessments are done every 3 months for the first two years (yrs). The primary endpoint is failure-free survival (FFS) at 2 yrs from the start of CRT, with failure defined as local or systemic disease recurrence. Secondary endpoints include toxicity and quality of life (QOL) assessments. We have planned correlative studies on peripheral blood and tumor tissue. We performed a protocol-defined interim safety and efficacy analysis to assess the 6-month FFS rate with CRT and adjuvant nivolumab. Results: From 8/03/2017 to 9/28/2021, 20 patients were enrolled at two centers; median age is 76 yrs, clinical stage range is T2-T4b, N0-N+, M0; the median number of nivolumab cycles is 6.5, and the median follow-up is 8.9 months. The estimated 6-month FFS rate is 88.2% (95% CI 74.2% - 100%). Disease has progressed in 9 patients, of which 4 have local bladder recurrence (T1 in 3/4) and 5 have distant metastases. The estimated median FFS is 17.1 months (95% CI 8.71 months - infinity). Grade ≥3 treatment-related adverse events (AEs) are noted in 3/20 patients (15%): elevated transaminases, diarrhea, and polymyalgia rheumatica. Grade 3 radiation therapy oncology group (RTOG) AEs occurred in 2 patients. QOL measures are serially evaluable in 13 patients for the first 3 months of adjuvant nivolumab, and are stable in the domains of disease-related physical symptoms, treatment side effects, and function/well-being, while are significantly improved (p=0.023) in the domain of disease-related emotional symptoms. Conclusions: In this first report of the role of immunotherapy adjuvant to CRT for localized bladder cancer, adjuvant nivolumab is well tolerated and has promising efficacy. Clinical trial information: NCT03171025.