A prospective phase II trial of neoadjuvant sintilimab in muscle-invasive urothelial carcinoma of bladder.

509 Background: To assess the efficacy and safety of the PD-1 antibody in neoadjuvant setting of muscle-invasive urothelial carcinoma of bladder (MIBC). Methods: In this prospective phase II trial (ChiCTR2000032730), eligible patients were cT2-T4 N0 MIBC, and were considered eligible for radical cystectomy (RC). Patients received sintilimab 200 mg on days 1, study treatment was repeated every 21 days up to 3 cycles before surgery. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included incidence of surgical related delayed events, relapse free survival, overall survival and safety. Results: Between Aug 2020 and Sep 2022, 15 patients (median age: 69, male 93.3%, PS=1 100%) were enrolled. The majority of patients (93.3%) completed the planned (median, 3; range 2 to 4) cycles of sintilimab without significant toxicities. The most common adverse events included hematuria (3/15), proteinuria (2/15), hypophosphatemia (2/15), hypoalbuminemia (2/15) and dysuria (2/15). Among the 15 patients who completed study treatment, 9 patients (60.0%) received RC. Among 6 patients who did not revive RC, 1 due to myasthenia gravis related to sintilimab, 1 due to progression disease, 3 patients refused RC due to bladder preserving, and 1 due to cardiac comorbidity unrelated to sintilimab. Pathologic results revealed 6 pCR (ypT0, 66.7%), 1 ypT0N1, 1 ypT2N0 and 1ypT4N0. At a median follow up of 181 days, they all had no disease recurrence and median DFS was not reached. 2 patients died of disease progression (1 refused RC, 1 had PD before RC). Conclusions: Neoadjuvant sintilimab was feasible and provided meaningful pathologic responses in patients with MIBC. Clinical trial information: ChiCTR2000032730 .