The United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA) has approved toripalimab (Loqtorzi) in combination with cisplatin and gemcitabine for the frontline treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) that is not amenable to surgery or radiotherapy. The MHRA has also approved toripalimab in combination with cisplatin and paclitaxel for the frontline treatment of adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).
The approval for NPC is based on the phase 3 JUPITER-02 trial, a randomized, double-blind, placebo-controlled, multinational, multicenter study. The trial investigated toripalimab plus gemcitabine and cisplatin versus placebo plus gemcitabine and cisplatin in the frontline setting for patients with recurrent or metastatic NPC. At a median survival follow-up of 36.0 months, toripalimab plus chemotherapy (n = 146) reduced the risk of disease progression by 48% and the risk of death by 37% compared with placebo plus chemotherapy (n = 143). The median progression-free survival (PFS) was 21.4 months (95% CI, 11.7-not evaluable) in the toripalimab arm versus 8.2 months (95% CI, 7.0-9.8) in the chemotherapy arm (HR, 0.52; 95% CI, 0.37-0.73; nominal P < .001). The median overall survival (OS) was not evaluable (95% CI, 38.7-not evaluable) with toripalimab versus 33.7 months (95% CI, 27.0-44.2) with placebo (HR, 0.63; 95% CI, 0.45-0.89; 2-sided P = .008).
Patients in the toripalimab arm achieved a higher overall response rate of 78.8% (95% CI, 71.2%-85.1%), including a complete response rate of 26.7%. In the placebo arm, the overall response rate was 67.1% (95% CI, 58.8%-74.8%) with a complete response rate of 13.3%. The median duration of response was 18.0 months (95% CI, 10.5-NE) in the toripalimab arm versus 6.0 months (95% CI, 5.6-8.3) in the placebo arm (HR, 0.49; 95% CI, 0.33-0.72).
Long-term follow-up data presented at the 2024 ASCO Annual Meeting showed that the 5-year OS rate with toripalimab plus chemotherapy was 52.0% versus 33.9% with placebo plus chemotherapy. The JUPITER-02 investigators observed no new safety signals with toripalimab plus chemotherapy.
The approval for ESCC was based on the phase 3 JUPITER-06 trial, a randomized, double-blind, placebo-controlled, multicenter study evaluating toripalimab plus paclitaxel and cisplatin versus placebo plus paclitaxel and cisplatin in the frontline advanced ESCC setting. At median follow-ups of 7.4 months and 7.3 months in the toripalimab (n = 257) and placebo (n = 257) arms, respectively, toripalimab plus chemotherapy generated superior PFS and OS outcomes versus placebo plus chemotherapy. In the respective arms, the median PFS was 5.7 months (95% CI, 5.6-7.0) and 5.5 months (95% CI, 5.2-5.6; HR, 0.58; 95% CI, 0.461-0.738; P < .00001) and the median OS was 17.0 months (95% CI, 14.0-NE) versus 11.0 months (95% CI, 10.4-12.6; HR, 0.58; 95% CI, 0.425-0.783; P = .00036). Survival benefits were significantly greater in the toripalimab versus placebo arm, regardless of PD-L1 status. However, adverse effects (AEs) leading to discontinuation of toripalimab/placebo, immune-related AEs, and grade 3 or higher immune-related AEs were more frequently observed in the toripalimab arm.
"The approval of toripalimab by the MHRA marks another significant milestone for toripalimab in Europe, not only making toripalimab the first and only drug in the UK for the treatment of [patients with] NPC, but also the only first-line treatment for ESCC, regardless of PD-L1 status," said Jianjun Zou, MD, PhD, general manager and chief executive officer of Junshi Biosciences.
Previously, on October 27, 2023, the FDA approved toripalimab-tpzi (Loqtorzi) in combination with cisplatin and gemcitabine for the frontline treatment of adult patients with metastatic or recurrent locally advanced NPC, as well as toripalimab monotherapy for the treatment of adult patients with recurrent, unresectable or metastatic NPC with progressive disease on or after receiving platinum-containing chemotherapy.
