1882O RENOTORCH: Toripalimab combined with axitinib versus sunitinib in first-line treatment of advanced renal-cell carcinoma (RCC) - A randomized, open-label, phase III study

Anti-PD-1 antibody plus antiangiogenic therapy can play a synergistic antitumor role in the treatment of advanced renal cancer. Toripalimab is a humanized monoclonal antibody against PD-1. Here, we report the results of a randomized, open label, phase 3 trial (NCT04394975) comparing toripalimab plus axitinib with sunitinib as first-line treatment for advanced RCC patients (pts). Eligible pts had untreated unresectable or metastatic clear cell RCC and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria. Pts were randomized in a 1:1 ratio to receive toripalimab (240mg) intravenously once every 3 weeks plus axitinib (5mg) orally twice daily or sunitinib (50mg) orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle). The primary endpoint was progression-free survival (PFS) assessed by the blinded independent central review per RECIST version 1.1. A total of 421 pts were randomized: 210 to the toripalimab plus axitinib arm and 211 to the sunitinib arm. After a median follow-up of 14.6 months, a significant improvement in median PFS was detected for the toripalimab plus axitinib arm compared to the sunitinib arm (18.0 vs. 9.8 months, HR = 0.66 [95% CI: 0.49-0.87], P = 0.0034). The 1-year PFS rates were 62.5% and 45.4%, respectively. The objective response rate (ORR) was 56.7% (95% CI: 49.7-63.5) for the toripalimab plus axitinib arm versus 30.8% (95% CI: 24.6-37.5) for the sunitinib arm (P＜ 0.0001). The median overall survival was not reached in the toripalimab plus axitinib arm and 26.8 months in the sunitinib arm (HR = 0.61 [95% CI: 0.40-0.92], P = 0.0186). The incidence of Grade ≥ 3 adverse events (AEs) (71.2% vs 67.1%), AEs leading to discontinuation of treatment (14.4% vs 8.1%), and fatal AEs (1.0% vs 1.0%) were similar between two arms. Among patients with previously untreated advanced RCC, treatment with toripalimab plus axitinib resulted in significantly longer PFS, as well as a higher ORR, than treatment with sunitinib. These results support the use of toripalimab with axitinib as a first-line treatment for advanced RCC.