CHMP Recommends Toripalimab Plus Chemo for Metastatic Nasopharyngeal Carcinoma and Advanced ESCC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended the approval of toripalimab-tpzi (Loqtorzi) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with nasopharyngeal carcinoma (NPC) that is recurrent, not amenable to surgery or radiotherapy, or metastatic; as well as the approval of toripalimab in combination with cisplatin and paclitaxel for the first-line treatment of adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).¹

The recommendation for the NPC indication is based on data from the phase 3 JUPITER-02 trial (NCT03581786), and the positive opinion regarding the ESCC indication is supported by findings from the phase 3 JUPITER-06 trial (NCT03829969).

“As a leading innovative pharmaceutical company in China, Junshi Biosciences is dedicated to addressing the clinical needs of local patients [and] offering novel therapies that provide survival benefits to patients globally,” Jianjun Zou, MD, PhD, general manager and chief executive officer of Junshi Biosciences, stated in a news release. “Currently, patients with NPC and ESCC in Europe receive limited clinical benefits from existing treatments. Toripalimab has the potential to improve their treatment options. The positive opinion from the CHMP brings us one step closer to this goal. We will continue communicating with local regulatory authorities so that our innovative therapy can benefit more European patients as soon as possible.”

In October 2023, the FDA approved toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with metastatic or recurrent locally advanced NPC, and as monotherapy for the treatment of adult patients with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy.²

JUPITER-02

The international, multicenter, randomized, double-blind JUPITER-02 trial enrolled patients with recurrent or metastatic NPC who had received no prior systemic chemotherapy in the recurrent/metastatic setting. Findings showed that patients treated with toripalimab plus chemotherapy (n = 146) experienced a median progression-free survival (PFS) of 21.4 months compared with 8.2 months for those given placebo plus chemotherapy (n = 143; HR, 0.52; 95% CI, 0.37-0.73; nominal P < .001). The 1- and 2-year PFS rates in the toripalimab arm were 59.0% and 44.8%, respectively. These respective rates were 32.9% and 25.4% for the placebo arm.³

Investigators enrolled patients between 18 and 75 years of age with histologically or cytologically confirmed primary recurrent or metastatic NPC that was not amenable for locoregional or curative treatment. Patients were randomly assigned 1:1 to receive 240 mg of toripalimab on day 1 plus 1000 mg/m2 of gemcitabine on days 1 and 8, and 80 mg/m2 of cisplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by toripalimab monotherapy at 240 mg once every 3 weeks as maintenance; or placebo plus the same gemcitabine/cisplatin regimen for up to 6 cycles, followed by placebo maintenance once every 3 weeks. Treatment continued for up to 2 years or until disease progression, unacceptable toxicity, or withdrawal of consent.

PFS by blinded independent central review (BICR) assessment per RECIST v1.1 criteria served as the trial’s primary end point. Secondary end points included objective response rate (ORR), overall survival (OS), investigator-assessed PFS, duration of response (DOR), and safety.

Additional data showed that at a median follow-up of 39.6 months (range, 1.2-47.4) for the toripalimab arm and 39.9 months (range, 0.2-48.3) for the placebo arm, the median OS was not reached (NR) for the toripalimab arm vs 33.7 months for the placebo arm (HR, 0.63; 95% CI, 0.45-0.89; 2-sided P = .008).

The BICR-assessed ORR was 78.8% for patients in the toripalimab group vs 67.1% for those in the placebo group, and the respective complete response rates were 26.7% and 13.3%. The median DOR was 18.0 months (95% CI, 10.5–not estimable) for the toripalimab arm vs 6.0 months (95% CI, 5.6-8.3) for the chemotherapy arm (HR, 0.49; 95% CI, 0.33-0.72).

Regarding safety, the rates of any-grade treatment-emergent adverse effects (TEAEs; toripalimab arm, 100%; placebo arm, 100%), grade 3 or higher TEAEs (89.7%; 90.2%), fatal TEAEs (3.4%; 2.8%), serious AEs (43.8%; 43.4%), and infusion reactions (4.1%; 4.2%) were similar between the 2 arms. The toripalimab regimen was associated with higher rates of AEs leading to discontinuation of toripalimab or placebo (11.6%; 4.9%), immune-related AEs (54.1%; 21.7%), and grade 3 or higher immune-related AEs (9.6%; 1.4%).

JUPITER-06

The multicenter, randomized, double-blind, placebo-controlled JUPITER-06 trial enrolled patients with locally advanced, recurrent, or metastatic ESCC who had received no prior systemic therapy in the advanced setting or had experienced disease relapse at least 6 months following the completion of perioperative chemotherapy/chemoradiotherapy. Findings showed that at a median follow-up of 7.1 months, patients treated with toripalimab plus chemotherapy (n = 257) achieved a median PFS of 5.7 months (95% CI, 5.6-7.0) vs 5.5 months (95% CI, 5.2-5.6) for those given placebo plus chemotherapy (n = 257; HR, 0.58; 95% CI, 0.46-0.74; 2-sided P < .0001). The 1-year PFS rates were 27.8% (95% CI, 20.4%-35.8%) and 6.1% (95% CI, 2.2%-12.6%), respectively.⁴

The median OS was 17 months (95% CI, 14.0-NR) in the toripalimab arm vs 11 months (9%% CI, 10.4-12.6) in the placebo arm (HR, 0.58; 95% CI, 0.43-0.78; 2-sided P = .0004).

To enroll, patients needed to be between 18 and 75 years of age with histologically or cytologically confirmed, locally advanced, recurrent, or metastatic ESCC. Other key inclusion criteria consisted of an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; adequate organ function; and at least 1 measurable lesion per RECIST v1.1 criteria.

Patients were randomly assigned 1:1 to receive toripalimab or placebo plus paclitaxel and cisplatin once every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance.

BICR-assessed PFS per RECIST v1.1 criteria and OS served as the trial’s coprimary end points. Secondary end points included ORR, DOR, disease control rate, and safety.

Safety data showed that 99.2% of patients in both arms experienced at least 1 any-grade TEAE. The rates of grade 3 or higher TEAEs were 73.2% for the toripalimab arm vs 70.0% for the placebo arm. Fatal TEAEs were reported in 8.2% of patients in both arms; the rates of fatal AEs deemed related to study treatment were 0.4% for the toripalimab arm vs 1.2% for the placebo arm.

References

1. Junshi Biosciences announces positive opinion from the European Medicines Agency’s CHMP for toripalimab. News release. Junshi Biosciences. July 26, 2024. Accessed July 29, 2024. https://www.globenewswire.com/news-release/2024/07/26/2919683/0/en/Junshi-Biosciences-Announces-Positive-Opinion-from-the-European-Medicines-Agency-s-CHMP-For-Toripalimab.html
2. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. FDA. October 27, 2023. Accessed July 29, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma
3. 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
4. Wang ZX, Cui C, Yao J, et al. Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): a multi-center phase 3 trial. Cancer Cell. 2022;40(3):277-288.e3. doi:10.1016/j.ccell.2022.02.007