Toripalimab Approved for First-Line Treatment of Patients With Nasopharyngeal Carcinoma

The US Food and Drug Administration (FDA) has granted approval to toripalimab-tpzi with cisplatin and gemcitabine for the treatment of patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma in the first-line setting; and toripalimab as a single-agent for patients with recurrent unresectable or metastatic nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy.

This regulatory decision was based on efficacy results from the multicenter, single-region, double-blind phase 3 JUPITER-02 trial as well as the open label, multicohort, phase 1b/2 POLARIS-02 trial.

In the JUPITER-02 study, 289 patients with metastatic/recurrent, locally advanced nasopharyngeal carcinoma who had not received prior systemic chemotherapy for recurrent or metastatic disease were randomized on a 1-to-1 basis to receive either toripalimab plus cisplatin and gemcitabine followed by toripalimab monotherapy, or placebo plus cisplatin and gemcitabine followed by placebo. The primary end point was progression-free survival (PFS) with overall survival (OS) as an additional end point.

There was a statistically significant improvement of PFS seen in the toripalimab arm compared with the placebo arm, with the median PFS with toripalimab as 11.7 months and with placebo as 8.0 months (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36 to 0.74; P = .0003). There was also a significant improvement observed in OS (not reached vs 33.7 months; HR, 0.63; 95% CI, 0.45 to 0.89; P = .0083)

In the POLARIS-02 trial, 172 patients with unresectable or metastatic nasopharyngeal who had received prior platinum-based chemotherapy or had disease progression within 6 months of completion of platinum-based chemotherapy administered as neoadjuvant, adjuvant, or definitive chemoradiation treatment for locally advanced disease were treated with toripalimab. The major outcomes were confirmed overall response rate (ORR) and duration of response (DOR). The ORR was 21% and the median DOR was 14.9 months.

Immune-mediated adverse reactions seen with toripalimab included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions related to toripalimab plus cisplatin and gemcitabine, that occurred in ≥20% of patients, were nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise. The most common adverse reactions related toripalimab as monotherapy were fatigue, hypothyroidism, and musculoskeletal pain.

The FDA recommends 240mg toripalimab-tpzi every 3 weeks, with cisplatin and gemcitabine, until disease progression, unacceptable toxicity, or up to 24 months. The recommended dose for previously treated nasopharyngeal carcinoma is 3 mg/kg toripalimab monotherapy every 2 weeks until disease progression or unacceptable toxicity.

Source:

US Food and Drug Administration. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. October 30, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma