Penpulimab-kcqx Approved for Non-Keratinizing Nasopharyngeal Carcinoma
Expert Perspectives · Lyn Brook · 2025-04-30
The FDA has approved penpulimab-kcqx (Akeso Biopharma Co., Ltd.) in combination with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). Additionally, penpulimab-kcqx received approval as a single agent for adults with metastatic non-keratinizing NPC who have experienced disease progression following platinum-based chemotherapy and at least one other prior line of therapy.
Why This Approval Matters
The approval of penpulimab-kcqx, both in combination with platinum-based chemotherapy and as a single agent, provides a new, evidence-based treatment option for patients with recurrent or metastatic non-keratinizing NPC. This decision addresses an unmet need for effective therapies in this patient population, particularly for those who have progressed after multiple lines of treatment.
Breaking Down the Trials
The efficacy of penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine was established in Study AK105-304 (NCT04974398), a double-blind, multicenter trial involving 291 patients with recurrent or metastatic NPC who had not previously received systemic chemotherapy for their advanced disease. Patients were randomized 1:1 to receive either penpulimab-kcqx with chemotherapy or placebo with chemotherapy, followed by maintenance with either penpulimab-kcqx or placebo. For details on chemotherapy regimens, refer to the full prescribing information.
The primary efficacy end point was progression-free survival (PFS), as assessed by a Blinded Independent Review Committee (BICR) using RECIST v1.1 criteria. A key secondary end point evaluated was overall survival (OS). Median PFS was 9.6 months in the penpulimab-kcqx arm compared to 7.0 months in the placebo arm. At 12-month follow-up, 31% of patients in the penpulimab-kcqx arm remained alive and progression-free, versus 11% in the placebo arm. Overall survival data were immature at the time of analysis, with 70% of prespecified deaths reported, but no detrimental trend was observed.
For single-agent use, efficacy was evaluated in Study AK105-202 (NCT03866967), an open-label, multicenter, single-arm trial enrolling 125 patients with unresectable or metastatic non-keratinizing NPC who had progressed after platinum-based chemotherapy and at least one additional line of therapy. The objective response rate (ORR) was 28%, and the median duration of response (DOR) was not reached.
Managing Adverse Events
Immune-mediated adverse events associated with penpulimab-kcqx included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin reactions. The most common adverse events experienced by ≥20% of patients receiving the combination regimen were nausea, vomiting, hypothyroidism, constipation, decreased appetite, weight loss, cough, COVID-19 infection, fatigue, rash, and pyrexia. For single-agent therapy, hypothyroidism and musculoskeletal pain were most common. Fatal adverse reactions occurred in 1% of patients, including pneumonitis, septic shock, colitis, and hepatitis.
Conclusion
The FDA approval of penpulimab-kcqx marks an important advancement in the treatment landscape for recurrent or metastatic non-keratinizing nasopharyngeal carcinoma. By demonstrating significant improvements in progression-free survival and offering a new option for patients who have exhausted prior therapies, penpulimab-kcqx provides clinicians with a valuable immunotherapy-based treatment.
Dosing and Administration
The recommended dose of penpulimab-kcqx with cisplatin or carboplatin and gemcitabine is 200 mg every three weeks, for up to 24 months, continued until disease progression or unacceptable toxicity. For previously treated NPC, the recommended single-agent dose is 200 mg every two weeks, for up to 24 months or until progression or unacceptable toxicity.