JUPITOR-02: Randomized, Double-Blind, Phase 3 Study of Toripalimab or Placebo Plus Cisplatin and Gemcitabine 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 (RM) Nasopharyngeal Carcinoma (NPC). Toripalimab, a humanized monoclonal antibody specific for human programmed death-1 (PD-1), provided durable responses in patients with RM-NPC in the second line+ setting. Methods: In this international phase III trial, 289 patients with RM-NPC with no prior chemotherapy in the RM setting were randomized (1:1) to receive either toripalimab or placebo in combination with GP every 3 weeks for up to 6 cycles, followed by monotherapy with toripalimab or placebo until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee per RECIST v1.1.RESULTSAt interim analysis, a significant improvement in PFS was detected in the toripalimab arm than the placebo arm, median PFS 11.7 vs. 8.0 months, HR=0.52 (95% CI: 0.36-0.74), p=0.0003. As of February 18, 2021, a 40% reduction in risk of death was observed in the toripalimab arm than the placebo arm, HR=0.603 (95% CI: 0.364 to 0.997). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%), and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS and OS than GP alone with a manageable safety profile. Trial Registration: NCT number NCT03581786. Funding: Shanghai Junshi Biosciences Co., LTD, Shanghai, China. Declaration of Interest: Hui Feng and Sheng Yao are employed by Shanghai Junshi Bioscience and TopAlliance Biosciences. Patricia Keegan is employed by TopAlliance Biosciences. Rui-hua Xu has served in a consulting or an advisory role for Bristol-Myers Squibb, Merck Serono, Roche, Astellas, AstraZeneca. The rest of authors have no disclosures of potential conflicts of interests. Ethical Approval: This trial was conducted in full conformance with the ICH E6 guideline for Good Clinical Practice (GCP) and the principles of the Declaration of Helsinki.