Abstract CT226: Final progression-free survival analysis of JUPITER-02, a randomized, double-blind, phase 3 study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma

Background: Gemcitabine-Cisplatin (GP) chemotherapy is the standard first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, in combination with GP chemotherapy showed significant improvement in progression-free survival (PFS) as first-line treatment for RM-NPC at the interim analysis of the JUPITER-02 study (NCT03581786), a randomized, placebo-controlled, double-blinded international Phase III trial. Here we report the results of the final PFS analysis and the interim overall survival (OS) analysis. Methods: Patients (n=289) with advanced NPC with no prior chemotherapy in the recurrent or metastatic setting were randomized (1:1) to receive toripalimab 240 mg (n=146) or placebo (n=143) in combination with gemcitabine and cisplatin every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Tumor response was assessed by a blinded independent review committee (BIRC) per RECIST v1.1. The primary endpoint was PFS by BIRC in the intention-to-treat population. Secondary end points included PFS by investigator, OS, objective response rate (ORR), duration of response (DOR) and safety. Results: At the final PFS analysis, the median follow-up time was 22.1 months for the toripalimab arm and 21.4 months for the placebo arm by the cut-off date of June 8, 2021. The toripalimab arm had a significantly longer PFS than the placebo arm as assessed by BIRC: median PFS 21.4 vs. 8.2 months, HR=0.52 (95% CI: 0.37-0.73), two-sided p<0.0001. The 1-year PFS rates were 59.0% vs. 32.9%. The ORR was 78.8% vs. 67.1% (P=0.022) and the median DOR was 18.0 vs. 6.0 months, HR= 0.49 (95% CI: 0.33-0.72). Consistently, PFS as assessed by investigator was also significantly longer in the toripalimab arm than the placebo arm: median PFS 17.3 vs. 8.1 months, HR=0.43 (95% CI: 0.31-0.58), P<0.0001. As of June 8, 2021, the median OS was not reached in either arm, with a trend favoring the toripalimab arm, HR=0.59 (95% CI: 0.37-0.94), P=0.024. The improvements of PFS and OS in the toripalimab arm were observed across key subgroups, including PD-L1 expression subgroups. Notably, dynamic decrease of plasma Epstein-Barr Virus DNA copy number from baseline was associated with favorable response. No new safety signal was identified. The incidence of Grade ≥3 adverse events (AEs) (89.7% vs 90.2%) and fatal AEs (2.7% vs 2.8%) were similar between the two arms; however, investigator-determined immune-related AEs (irAEs) (53.4% vs. 21.7%) and Grade ≥3 irAEs (8.9% vs. 1.4%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as first-line treatment for advanced NPC had a manageable safety profile and provided superior PFS with a favorable trend in overall survival than chemotherapy alone. Citation Format: Hai-Qiang Mai, Qiu-Yan Chen, Dongping Chen, Chaosu Hu, Kunyu Yang, Jiyu Wen, Jingao Li, Yingrui Shi, Feng Jin, Ruilian Xu, Jianji Pan, Shenhong Qu, Ping Li, Chunhong Hu, Yi-Chun Liu, Yi Jiang, Xia He, Hung-Ming Wang, Wan-Teck Lim, Rui-Hua Xu, Coherus Biosciences and Shanghai Junshi Biosciences. Final progression-free survival analysis of JUPITER-02, a randomized, double-blind, phase 3 study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT226.