On October 27, the U.S. Food and Drug Administration (FDA) approved toripalimab-tpzi (Loqtorz) with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma. The FDA also approved toripalimab-tpzi as a single agent for adults with recurrent unresectable or metastatic nasopharyngeal carcinoma with disease progression on or after a platinum-containing chemotherapy.
JUPITER-02
Efficacy of toripalimab-tpzi with cisplatin and gemcitabine was evaluated in JUPITER-02 (ClinicalTrials.gov identifier NCT03581786), a randomized, multicenter, single-region, double-blind, placebo-controlled trial in 289 patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients were randomly assigned 1:1 to receive either toripalimab-tpzi with cisplatin and gemcitabine followed by toripalimab-tpzi, or placebo with cisplatin and gemcitabine followed by placebo.
The primary efficacy outcome measure was progression-free survival as assessed by a blinded independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Overall survival was an additional endpoint.
A statistically significant progression-free survival improvement was observed with a median progression-free survival of 11.7 months vs 8.0 months (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.36–0.74, P = .0003) for the toripalimab-tpzi and placebo-containing regimens, respectively. A statistically significant overall survival improvement was also observed, with median overall survival not reached (95% CI = 38.7 months to not estimable) for the toripalimab-tpzi–containing regimen and 33.7 months (95% CI = 27.0–44.2 months) for the placebo-containing regimen (HR = 0.63, 95% CI = 0.45–0.89, P = .0083).
POLARIS-02
Efficacy of toripalimab-tpzi as a single agent was evaluated in POLARIS-02 (NCT02915432), an open-label, multicenter, single-country, multicohort trial in 172 patients with unresectable or metastatic nasopharyngeal carcinoma 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 for locally advanced disease. Patients received toripalimab-tpzi until disease progression per RECIST version 1.1 or unacceptable toxicity.
The major efficacy outcome measures were confirmed overall response rate and duration of response as assessed by a blinded independent review committee using RECIST version 1.1. Overall response rate was 21% (95% CI = 15%–28%) and median duration of response was 14.9 months (95% CI = 10.3 months to not estimable).
Immune-mediated adverse reactions occurred with toripalimab-tpzi, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) for toripalimab-tpzi in combination with cisplatin and gemcitabine 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 (≥ 20%) for toripalimab-tpzi as a single agent were fatigue, hypothyroidism, and musculoskeletal pain.
The recommended toripalimab-tpzi dose with cisplatin and gemcitabine is 240 mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended toripalimab-tpzi dose as a single agent for previously treated nasopharyngeal carcinoma is 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.
