Efficacy, Safety, and Biomarker Analysis of Toripalimab Monoclonal Antibody Combined with Gemcitabine and Cisplatin Chemotherapy as Neoadjuvant Treatment in Muscle-Invasive Bladder Cancer: A Phase II Clinical Trial.

[PURPOSE] To evaluate the efficacy and safety of Toripalimab combined with gemcitabine and cisplatin (GC) as the neoadjuvant treatment (NAT) before radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC).

[MATERIALS AND METHODS] This phase II trial enrolled 30 patients with T2-3N0M0 MIBC scheduled for RC. Patients received a treatment regimen of toripalimab 240 mg, gemcitabine 1000 mg/m, and cisplatin 70 mg/m on day 1, followed by gemcitabine 1000 mg/m on day 8, in 21-day cycles for a total of 4 cycles. RC was scheduled 4 to 6 weeks after the last treatment cycle. The primary end point is the pathological complete response (pCR), and the secondary end points are safety, overall survival (OS), and progression-free survival (PFS). The FISHER test was performed to analyze the relationship between genomic changes, tumor mutation burden (TMB), and pCR rate.

[RESULTS] From January 2020 to December 2021, 27 patients underwent RC after NAT, and 3 withdrew from the study. The pCR rate reached 40.7% (11/27). The 1-year and 3-year PFS rates were 85.2% and 77.6%, respectively; the 1-year and 3-year OS rates were 96.2% and 84.6%, respectively. Among the 18 patients who retained the target lesions during NAT, the pCR rate was 27.8% (5/18), and the pathological response rate was 50.0% (9/18). The rate of adverse events of grade 3 or higher was 13.3%. Biomarker analysis indicated that patients with dual-mutation in KMT2D, ERBB2, or EPHA2 genes had a lower pCR rate following NAT. In the patients with PD-L1 expression ≥ 5% (n = 16), the pCR and pathological response rate were 43.8% (7/16) and 68.8% (11/16), respectively. In patients with PD-L1 expression < 5% (n = 11), the pCR rate was 36.4% (4/11) and the pathological response rate was 63.6% (7/11).

[CONCLUSIONS] Toripalimab combined with GC chemotherapy demonstrates a good efficacy and safety, making it a promising therapeutic strategy for NAT of MIBC.

[TRIAL REGISTRATION] The clinical trial number for this study is ChiCTR2100051298.