FDA Approves Penpulimab for Patients With Non-Keratinizing Nasopharyngeal Carcinoma
On April 23, 2025, the United States Food and Drug Administration (FDA) approved first-line penpulimab plus cisplatin or carboplatin and gemcitabine for patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma, based on results from the AK105-304 study. Additionally, the FDA approved penpulimab monotherapy for patients with mestatic non-keratinizing nasopharyngeal carcinoma who progressed on or after platinum-based chemotherapy and at least 1 other prior line of therapy, based on results from the AK105-202 study.
The multicenter, double-blind AK105-304 study enrolled 291 patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma who had not received prior lines of systemic chemotherapy. Patients were randomized on a 1-to-1 basis to receive either penpulimab plus cisplatin/carboplatin and gemcitabine followed by penpulimab (penpulimab arm), or placebo plus cisplatin/carboplatin and gemcitabine followed by placebo (placebo arm). The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and safety.
At analysis, median PFS was 9.6 months in the penpulimab arm and 7 months in the placebo arm (hazard ratio [HR] 0.45; 95% confidence interval [CI], 0.33 to 0.62; P < .0001) with 31% of patients in the penpulimab arm and 11% of patients in the placebo arm alive and progression-free at 12-month follow up. OS results were immature at analysis with 70% of pre-specified deaths for the final analysis reported. No detrimental trend was observed.
Immune-related adverse events included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions occurring in ≥ 20% of patients included nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, caught, COVID-19, fatigue, rash, and pyrexia.
In the multicenter, open-label, single-arm AK105-202 trial, 125 patients with unresectable or metastatic non-keratinizing nasopharyngeal carcinoma who experienced disease progression after platinum-based chemotherapy and 1 other prior line of therapy received penpulimab for up to 24 months or until disease progression or unacceptable toxicity. Primary end points included objective response rate (ORR) and duration of response. A key secondary end point was safety.
At analysis, the ORR was 28% and the median duration of response was not reached. The most common adverse reactions occurring in ≥ 20% of patients included hypothyroidism and musculoskeletal pain. Fatal adverse reactions including pneumonitis, septic shock, colitis, and hepatitis occurred in 1% of patients.
The recommended dose of penpulimab with cisplatin or carboplatin and gemcitabine is 200 mg once every 3 weeks for up to 24 months or until disease progression or unacceptable toxicity. The recommended dose of single agent penpulimab is 200 mg once every 2 weeks for up to 24 months or until disease progression or unacceptable toxicity.
Source:
FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma. Accessed on April 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma
