Toripalimab NDA Under Review in Hong Kong for Nasopharyngeal Carcinoma

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The Drug Office, Department of Health, the Government of the Hong Kong Special Administrative Region has accepted a new drug application (NDA) seeking the approval of toripalimab-tpzi (Loqtorzi) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma, and as monotherapy for the treatment of adult patients with recurrent, unresectable, or metastatic nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy.¹

The NDA is supported by data from the phase 3 JUPITER-02 trial (NCT03581786), which evaluated toripalimab plus gemcitabine and cisplatin for the first-line treatment of patients with nasopharyngeal carcinoma, as well as the phase 2 POLARIS-02 (NCT02915432), which investigated single-agent toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma in the second line and beyond.

Findings from JUPITER-02 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 patients treated with placebo plus chemotherapy (n = 143; HR, 0.52; 95% CI, 0.37-0.73). Furthermore, the median overall survival (OS) was not reached in the toripalimab group vs 33.7 months in the placebo group (HR, 0.63; 95% CI, 0.45-0.89; 2-sided P = .008) at a median survival follow-up of 36 months.²

In POLARIS-02, patients treated with toripalimab monotherapy (n = 190) achieved an overall response rate (ORR) of 20.5% and a median duration of response (DOR) of 12.8 months. The median PFS was 1.9 months, and the median OS was 17.4 months.³

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 nasopharyngeal carcinoma, and as monotherapy for the treatment of adult patients with recurrent, unresectable, or metastatic nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy. The regulatory decision was also supported by data from JUPITER-02 and POLARIS-02.⁴

JUPITER-02

The international, multicenter, randomized, double-blind, phase 3 study enrolled patients with recurrent or metastatic nasopharyngeal carcinoma who received no prior systemic chemotherapy in the recurrent or metastatic setting.²

Patients were randomly assigned 1:1 to receive 240 mg of toripalimab or placebo once every 3 weeks in combination with 1000 mg/m² of gemcitabine on days 1 and 8 and 80 mg/m² of cisplatin on day 1 of each 3-week cycle. Chemotherapy was administered for up to 6 cycles, and toripalimab was continued for up to 2 years.⁵

Independent review committee–assessed PFS served as the trial’s primary end point. Secondary end points included OS, investigator-assessed PFS, ORR, DOR, disease control rate, and patient-reported outcomes.

Additional data showed that OS was favored with the toripalimab regimen irrespective of PD-L1 expression.²

Regarding safety, patients in the experimental arm experienced higher rates of adverse effects (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%). Notably, rates of any-grade AEs, grade 3 or higher AEs, and fatal AEs were similar between the 2 arms.

POLARIS-02

The single-arm, multicenter, phase 2 trial included patients with recurrent or metastatic nasopharyngeal carcinoma that was refractory to standard chemotherapy. All patients received 3 mg/kg of toripalimab once every 2 weeks until confirmed disease progression or unacceptable toxicity.³

Along with the primary end point of ORR, the study’s secondary end points included safety, DOR, PFS, and OS.

Additional data showed that patients who progressed after at least 2 lines of systemic chemotherapy (n = 92) experienced an ORR of 23.9%. In patients with PD-L1–positive disease and PD-L1–negative disease, the ORRs were 27.1% and 19.4%, respectively (P = .31).

Any-grade treatment-related AEs (TRAEs) occurred in 74.2% of patients, and the rate of grade 3 or higher TRAEs was 14.2%. The most common any-grade TRAEs included hypothyroidism (23.7%), anemia (15.3%), increased aspartate aminotransferase (15.3%), increased alanine aminotransferase (13.7%), asthenia (13.2%), proteinuria (12.6%), leukopenia (10.0%), pyrexia (9.5%), pruritus (8.4%), rash (6.3%), and neutropenia (5.3%).

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 NDA acceptance in Hong Kong for toripalimab. News release. Junshi Biosciences. April 24, 2024. Accessed April 25, 2024. https://www.globenewswire.com/news-release/2024/04/25/2869233/0/en/Junshi-Biosciences-Announces-NDA-Acceptance-in-Hong-Kong-for-Toripalimab.html
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. 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
4. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. FDA. October 27, 2023. Accessed April 25, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma
5. The efficacy and safety study of toripalimab injection combined with chemotherapy for nasophapyngeal cancer. ClinicalTrials.gov. Updated April 18, 2022. Accessed April 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03581786