Toripalimab Plus Chemo Approved in UK for Frontline Nasopharyngeal Carcinoma and ESCC

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, as well as in combination with cisplatin and paclitaxel for the frontline treatment of adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).¹

The approval for patients with NPC was primarily supported by findings from the randomized, double-blind, placebo-controlled, multinational, multicenter, phase 3 JUPITER-02 trial (NCT03581786), which investigated toripalimab plus gemcitabine and cisplatin vs placebo plus gemcitabine and cisplatin in the frontline setting in patients with recurrent or metastatic NPC.^1,2 Data demonstrated that 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).² The median progression-free survival (PFS) was 21.4 months (95% CI, 11.7-not evaluable [NE]) in the toripalimab arm vs 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 NE (95% CI, 38.7-NE) with toripalimab vs 33.7 months (95% CI, 27.0-44.2) with placebo (HR, 0.63; 95% CI, 0.45-0.89; 2-sided P = .008).

Furthermore, patients in the toripalimab arm achieved a higher overall response rate, at 78.8% (95% CI, 71.2%-85.1%), including a complete response rate of 26.7%. In the placebo arm, these respective rates were 67.1% (95% CI, 58.8%-74.8%) and 13.3%. The median duration of response was 18.0 months (95% CI, 10.5-NE) in the toripalimab arm vs 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, which were presented at the 2024 ASCO Annual Meeting, showed that the 5-year OS rate with toripalimab plus chemotherapy was 52.0% vs 33.9% with placebo plus chemotherapy.³ Notably, the JUPITER-02 investigators observed no new safety signals with toripalimab plus chemotherapy.¹

The approval for patients with ESCC was primarily supported by findings from the randomized, double-blind, placebo-controlled, multicenter phase 3 JUPITER-06 trial (NCT03829969), which evaluated toripalimab plus paclitaxel and cisplatin vs 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 vs 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) vs 11.0 months (95% CI, 10.4-12.6; HR, 0.58; 95% CI, 0.425-0.783; P = .00036).⁴ Notably, survival benefits were significantly greater in the toripalimab vs 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,” Jianjun Zou, MD, PhD, general manager and chief executive officer of Junshi Biosciences, stated in a news release.¹ “We are extremely proud to introduce innovative Chinese biopharmaceuticals to Europe that can address longstanding unmet medical needs of the patients there. Moving forward, we will remain committed to our globalization strategy, ‘In China, For Global.’ We will continue working towards the commercialization of toripalimab, and offer high-quality, innovative, domestically developed medicines to benefit more patients around the world.”

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.⁵ 

References

1. Junshi Biosciences announces UK MHRA approval for marketing of toripalimab. News Release. Shanghai Junshi Biosciences Co., Ltd. November 18, 2024. Accessed November 18, 2024. https://www.biospace.com/press-releases/junshi-biosciences-announces-uk-mhra-approval-for-marketing-of-toripalimab
2. Mai HQ, Chen QY, Chen D, et al. Toripalimab plus chemotherapy for recurrent or metastatic nasopharyngeal carcinoma: the JUPITER-02 randomized clinical trial. JAMA. 2023;330(20):1961-1970. doi:10.1001/jama.2023.20181
3. 3.Chen QY, Mai HQ, Chen DP, et al. 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). J Clin Oncol. 2024;42(suppl 16):6039. doi:10.1200/JCO.2024.42.16_suppl.6039
4. Xu RH, Wang F, Cui C, et al. JUPITER-06: a randomized, double-blind, phase III study of toripalimab versus placebo in combination with first-line chemotherapy for treatment naive advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ann Oncol. 2021;32(suppl 5):S1041. doi:10.1016/j.annonc.2021.08.1482
5. Coherus and Junshi Biosciences announce FDA approval of Loqtorzi (toripalimab-tpzi) in all lines of treatment for recurrent or metastatic Nasopharyngeal carcinoma (NPC). News release. Coherus BioSciences and Shanghai Junshi Biosciences. October 27, 2023. Accessed November 18, 2024. https://investors.coherus.com/news-releases/news-release-details/coherus-and-junshi-biosciences-announce-fda-approval-loqtorzitm#:~:text=(Junshi%20Biosciences%2C%20HKEX%3A%201877,and%20as%20monotherapy%20for%20the