Toripalimab Wins Approval in India and Hong Kong for Recurrent/Metastatic Nasopharyngeal Carcinoma

Toripalimab (Zytorvi in India; Loqtorzi in Hong Kong) has been approved for marketing in India and China’s Hong Kong Special Administrative Region in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC), and as a single agent for the treatment of adult patients with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.¹

The frontline approval was supported by data from the phase 3 JUPITER-02 (NCT03581786), and the single-agent indication was based on data from the phase 2 POLARIS-02 trial (NCT02915432).

“As of now, toripalimab has been approved for marketing in over 30 countries and regions across 3 continents worldwide. With its differentiated clinical layout and outstanding clinical performance, it has brought a new treatment that can change the therapeutic landscape to local doctors and patients, which we are very excited about,” Jianjun Zou, MD, PhD, general manager and chief executive officer of Junshi Biosciences, stated in a news release. “Moving forward, we will continue to implement the company’s international strategy of ‘In China, For Global’ and work with partners to provide more overseas patients with high-quality innovative drugs from China.”

In October 2023, the FDA approved toripalimab-tpzi (Loqtorz) 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

In September 2024, the European Commission approved toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic NPC.³

JUPITER-02

Data from the international, multicenter, double-blind JUPITER-02 trial demonstrated that patients treated with toripalimab plus gemcitabine and cisplatin (n = 146) achieved a median progression-free survival (PFS) of 21.4 months (interquartile range [IQR], 7.1-not estimable [NE]) vs 8.2 months (IQR, 5.7-NE) for patients given placebo plus gemcitabine and cisplatin (n = 143; HR, 0.52; 95% CI, 0.37-0.73).⁴

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

Investigators enrolled patients between 18 and 75 years of age who had histologically or cytologically confirmed primary recurrent or metastatic NPC not amenable for locoregional or curative-intent treatment. Patients were not allowed to have received prior systemic chemotherapy in the recurrent or metastatic setting.

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

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

PFS per blinded independent central review assessment was the trial’s primary end point. Secondary end points comprised OS, overall response rate (ORR), investigator-assessed PFS, duration of response (DOR), and safety.

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 100% of patients in both arms. The rates of grade 3 or higher TEAEs were 89.7% for patients in the toripalimab arm vs 90.2% for patients in the placebo arm. Fatal TEAEs were reported in 3.4% and 2.8% of patients, respectively, and serious adverse effects (AEs) occurred at rates of 43.8% and 43.4%, respectively. Patients treated in the toripalimab arm experienced 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%).

POLARIS-02

Findings from the single-arm, multicenter POLARIS-02 study showed that patients with recurrent or metastatic NPC that was refractory to standard chemotherapy treated with single-agent toripalimab (n = 190) experienced an ORR of 20.5% (95% CI, 15.0%-27.0%) and a disease control rate (DCR) of 40.0% (95% CI, 33.0%-47.3%). Notably, 38.4% of patients achieved a decrease in target lesions from baseline. The median time to response was 1.8 months (95% CI, 1.8-2.1), and the median DOR was 12.8 months (95% CI, 9.4-NE).

In patients who responded (n = 39) or had stable disease (n = 38), the median OS was NR; Patients with progressive disease (n = 113) had a median OS of 8.4 months.

Investigators enrolled patients at least 18 years of age with histologically or cytologically documented recurrent or metastatic NPC that was refractory to prior standard chemotherapy, or those who experienced disease progression within 6 months of adjuvant chemotherapy or chemoradiotherapy. Patients needed to have measurable disease, an ECOG performance status of 0 or 1, and adequate organ function.

Toripalimab was administered to all patients at 3 mg/kg once every 2 weeks, and treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Patients were allowed to continue treatment after initial disease progression if they were still deriving clinical benefit in the opinion of the investigator and sponsor.

ORR by independent review committee assessment per RECIST 1.1 criteria served as the trial’s primary end point. Secondary end points consisted of safety, DOR, DCR, PFS, and OS.

Regarding safety, treatment-related AEs (TRAEs) were reported in 74.2% of patients, and the rate of grade 3 or higher TRAEs was 14.2%. Immune-related AEs included hypothyroidism (23.7%), hyperthyroidism (2.6%), abnormal liver function (1.6%), interstitial lung disease (1.6%), dermatomyositis (0.5%), and autoimmune myocarditis (0.5%).

References

1. Junshi Biosciences announces toripalimab obtained approval for marketing in India and China’s Hong Kong SAR. News release. Junshi Biosciences. October 15, 2024. Accessed October 15, 2024. https://www.biospace.com/press-releases/junshi-biosciences-announces-toripalimab-obtained-approval-for-marketing-in-india-and-chinas-hong-kong-sar
2. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. FDA. October 27, 2023. Accessed October 15, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma
3. Junshi Biosciences announces European Commission approval for marketing of toripalimab. News release. Junshi Biosciences. September 25, 2024. Accessed October 15, 2024. https://www.biospace.com/press-releases/junshi-biosciences-announces-european-commission-approval-for-marketing-of-toripalimab
4. 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
5. Wang FH, Wei XL, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase II clinical trial (POLARIS-02). J Clin Oncol. 2021;39(7):704-712. doi:10.1200/JCO.20.02712