Toripalimab Plus Chemo Wins European Approval for Nasopharyngeal Carcinoma and Esophageal Squamous Cell Carcinoma

The European Commission has approved toripalimab (Loqtorzi) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic nasopharyngeal carcinoma (NPC); and 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 approval for the NPC indication was supported by data from the phase 3 JUPITER-02 trial (NCT03581786). The ESCC approval was based on findings from the phase 3 JUPITER-06 trial (NCT03829969).

“Both NPC and [ESCC] are highly prevalent in Asia, while the development of innovative therapies for these cancer types has been slow in Europe and the Americas. The outstanding results from the JUPITER-02 and JUPITER-06 studies reflect the pioneering leadership of Chinese researchers in the diagnosis, treatment, and clinical research of NPC and [ESCC],” Ruihua Xu, MD, PhD, principal investigator and president of Sun Yat-sen University Cancer Center, stated in a news release. “We hope that this ‘Chinese Solution’ will truly transform the outlook for patients around the world who have long lacked effective treatment options for these cancers and bring them renewed hope for survival.”

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

Findings from the international, multicenter, double-blind trial showed that patients treated with toripalimab plus gemcitabine and cisplatin (n = 146) experienced a median progression-free survival (PFS) of 21.4 months (IQR, 7.1-not estimable [NE]) compared with 8.2 months (IQR, 5.7-NE) for those treated with placebo plus gemcitabine and cisplatin (n = 143; HR, 0.52; 95% CI, 0.37-0.73).³

At a median follow-up of 36.0 months, the median overall survival (OS) was not yet reached (NR; IQR, 27.6-NE) for the toripalimab regimen vs 33.7 months (IQR, 17.8-NE) for the placebo regimen (HR, 0.63; 95% CI, 0.45-0.89; 2-sided P = .008).

The study 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-intent treatment. No prior systemic chemotherapy in the recurrent or metastatic setting was allowed.

Patients were randomly assigned 1:1 to receive toripalimab at 240 mg on day 1, gemcitabine at 1000 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1 of each 3-week cycle for up to 6 cycles; or placebo plus the same regimen of gemcitabine and cisplatin for up to 6 cycles. Single-agent toripalimab at 240 mg or placebo was then given as maintenance once every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or for a maximum of 2 years.

Stratification factors included tumor status (recurrent vs primary metastatic) and ECOG performance status (0 vs 1).

Blinded independent central review (BICR)–assessed PFS served as the trial’s primary end point. Secondary end points included OS, overall response rate (ORR), investigator-assessed PFS, duration of response (DOR), and safety.

Regarding safety, the rates of any-grade treatment-emergent adverse effects (TEAEs) were 100% in both arms. Grade 3 or higher TEAEs occurred in 89.7% of patients in the toripalimab arm vs 90.2% of patients in the placebo arm. The respective rates of fatal TEAEs were 3.4% and 2.8%, and serious adverse effects (AEs) occurred at rates of 43.8% and 43.4%, respectively. The toripalimab regimen was associated with higher rates of AEs leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related AEs (54.1% vs 21.7%), and grade 3 or higher immune-related AEs (9.6% vs 1.4%).

JUPITER-06

Data from the multicenter, double-blind, placebo-controlled JUPITER-06 trial showed that, at a median follow-up of 7.1 months, patients treated with toripalimab plus chemotherapy (n = 257) experienced 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).⁴

Patients in the toripalimab arm achieved a median OS of 17 months (95% CI, 14.0-NR) vs 11 months (95% CI, 10.4-12.6) for those in the placebo arm (HR, 0.58; 95% CI, 0.43-0.78; 2-sided P = .0004).

Investigators enrolled patients between 18 and 75 years of age with histologically or cytologically confirmed, locally advanced, recurrent, or metastatic ESCC not amendable for curative esophagectomy or definitive chemoradiation. No prior systemic therapy for relapsed or metastatic disease was allowed; neoadjuvant or adjuvant chemotherapy with or without radiotherapy for nonmetastatic disease was allowed if patients experienced relapse after at least 6 months after the last dose of chemotherapy. 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 one measurable lesion per RECIST 1.1 criteria.

Patients were randomly assigned 1:1 to receive toripalimab at 240 mg or placebo on day 1 in combination with paclitaxel at 175 mg/m2 and cisplatin at 75 mg/m2 on day 1 of each 3-week cycle for up to 6 cycles, followed by toripalimab at 240 mg or placebo alone once every 3 weeks for up to 2 years. Treatment continued until progressive disease, intolerable toxicity, withdrawal of consent, or maximum treatment was reached.

BICR-assessed PFS and OS were the trial’s dual primary end points. Secondary end points included investigator-assessed PFS, ORR, DOR, disease control rate, 1- and 2-year PFS and OS, and safety.

Any-grade TEAEs occurred in 99.2% of patients in both arms. The rates of grade 3 or higher TEAEs were 73.2% for the toripalimab regimen vs 70.0% for the placebo regimen. 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 European Commission approval for marketing of toripalimab. News release. Junshi Biosciences. September 25, 2024. Accessed September 25, 2024. https://www.biospace.com/press-releases/junshi-biosciences-announces-european-commission-approval-for-marketing-of-toripalimab
2. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. FDA. October 27, 2023. Accessed September 25, 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