Final overall survival analysis of JUPITER-02: A phase 3 study of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

6009 Background: There are currently no FDA-approved IO therapies for NPC. Toripalimab in combination with Gemcitabine-Cisplatin (GP) chemotherapy had shown significant improvement over chemotherapy alone in progression-free survival (PFS) as first-line treatment for recurrent or metastatic (r/m) NPC at the interim PFS analysis of JUPITER-02 (NCT03581786) study. The final overall survival (OS) analysis results are summarized here. Methods: Patients with r/m NPC (n = 289) were randomized (1:1) to receive toripalimab 240 mg (n = 146) or placebo (n = 143) in combination with GP once 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 performance score (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. The primary endpoint was PFS by an independent review committee. Secondary endpoints included OS and safety. Results: By the cutoff date of Nov 18, 2022, when 133 events were reached for the final OS analysis, the median survival follow up was 30.1 months. A significant improvement in OS was observed for the toripalimab arm over the placebo arm: HR = 0.63 (95% CI: 0.45-0.89), two-sided p = 0.0083. The median OS was not reached in the toripalimab arm and was 33.7 months in the placebo arm. The 2-year and 3-year OS rates were 78.0% vs. 65.1%, and 64.5% vs. 49.2% respectively. A consistent effect on OS, favoring the toripalimab arm, was observed in nearly all subgroups, including PD-L1 high and PD-L1 low expression subgroups. No new safety signals were identified in the toripalimab arm since the interim report. The incidence of Grade ≥3 adverse events (AEs) (89.7% vs 90.2%) and fatal AEs (3.4% vs 2.8%) were similar between two arms. However, AEs leading to discontinuation of toripalimab/placebo (11.6% vs 4.9%), immune-related (irAEs) (54.1% vs. 21.7%) and Grade ≥3 irAEs (9.6% vs. 1.4%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1 st -line treatment for r/m NPC provided clinically important and highly significant OS advantage over GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786 .