Four-year overall survival follow-up and dynamic EBV titer analysis of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (r/m NPC).

6039 Background: In October 2023, the US FDA approved toripalimab in combination with Gemcitabine-Cisplatin (GP) as first-line treatment for recurrent or metastatic (r/m) NPC based on the results of JUPITER-02 study (NCT03581786). Here we report the results of four-year overall survival (OS) follow-up and dynamic EBV DNA copy number and its correlation with clinical outcome. 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 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). The primary endpoint was progression free survival by an independent review committee. Secondary endpoints included OS and safety. Exploratory endpoints included dynamic blood EBV DNA copy number and its correlation with clinical efficacy. Results: By the cutoff date of January 9, 2024, 50 months after the last patient was enrolled, 150 deaths were recorded. Compared with the results from the final OS analysis, consistent survival improvement was observed for toripalimab over placebo: HR=0.61 (95% CI: 0.44-0.85), nominal p=0.0027. The median OS was not yet reached in the toripalimab arm and was 33.7 months in the placebo arm. The 5-year OS rates were 52.0% in the toripalimab arm, and 33.9% in the placebo arm. Among patients with detectable baseline EBV DNA copy number and at least one EBV result after study treatment, significantly more patients from the toripalimab arm had EBV DNA copy number decreased to undetectable level than those in the placebo arm, 96.3% vs. 84.5%, p= 0.004. In addition, significantly less patients experienced EBV DNA copy number rebound in the toripalimab arm than in the placebo arm after the initial reduction, 36.5% vs, 57.4%, p=0.002. The median time from the lowest EBV DNA copy number to the rebound was 20.5 vs. 6.0 months in the toripalimab and placebo arms respectively. The rebound also preceded investigator-assessed disease progression by a median of 1.9 months in the toripalimab arm. Conclusions: The combination of toripalimab and chemotherapy showed long term survival benefit than chemotherapy alone with a 5-year OS rate at 52%. EBV DNA copy number might be used to monitor clinical response and predict disease progression. Clinical trial information: NCT03581786 .