Penpulimab-kcqx is approved by the USFDA for non-keratinizing nasopharyngeal carcinoma

On April 23, 2025, the Food and Drug Administration sanctioned penpulimab-kcqx (Akeso Biopharma Co., Ltd.) in conjunction with cisplatin or carboplatin and gemcitabine for the initial treatment of people with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC).

The FDA has approved penpulimab-kcqx as a monotherapy for people with metastatic non-keratinizing nasopharyngeal carcinoma who have seen disease progression following platinum-based chemotherapy and at least one additional course of treatment.

Effectiveness and Safety

The efficacy of penpulimab-kcqx in conjunction with cisplatin or carboplatin and gemcitabine was assessed in Study AK105-304 (NCT04974398), a randomized, double-blind, multi-center trial involving 291 patients with recurrent or metastatic nasopharyngeal carcinoma who had not previously undergone systemic chemotherapy for recurrent or metastatic disease. Patients were randomly assigned in equal groups to receive either penpulimab-kcqx with cisplatin or carboplatin and gemcitabine, followed by penpulimab-kcqx, or a placebo with cisplatin or carboplatin and gemcitabine, followed by a placebo. Chemotherapy protocols are detailed in the comprehensive prescribing information.

The principal effectiveness outcome measure was progression-free survival (PFS), evaluated by a Blinded Independent Review Committee in accordance with RECIST v1.1. Overall survival (OS) constituted a key secondary goal. The median progression-free survival (PFS) was 9.6 months (95% CI: 7.1, 12.5) for the penpulimab-kcqx group and 7.0 months (95% CI: 6.9, 7.3) for the placebo group, yielding a hazard ratio (HR) of 0.45 (95% CI: 0.33, 0.62) with a two-sided p-value of <0.0001.

After 12 months of follow-up, 31% of patients in the penpulimab-kcqx group and 11% in the placebo group remained alive and progression-free. Although overall survival findings were preliminary, with 70% of the predetermined fatalities for the final analysis documented, no adverse trend was detected.

The effectiveness of single-agent penpulimab-kcqx was assessed in Study AK105-202 (NCT03866967), an open-label, multicenter, single-arm trial conducted within one nation. The trial comprised 125 patients with unresectable or metastatic non-keratinizing nasopharyngeal carcinoma who experienced disease progression following platinum-based chemotherapy and at least one additional treatment regimen. Patients were administered penpulimab-kcqx until disease progression or intolerable toxicity, for a maximum duration of 24 months.

The primary efficacy outcome measures were the objective response rate (ORR) and the duration of response (DOR), evaluated according to RECIST v1.1 by an Independent Radiology Review Committee. The overall response rate (ORR) was 28% (95% confidence interval: 20, 37), and the median duration of response (DOR) was not attained (95% confidence interval: 9.2, not estimable).

Immune-mediated adverse reactions associated with penpulimab-kcqx included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal impairment, and dermatological adverse reactions. The predominant side events (≥20%) associated with penpulimab-kcqx in conjunction with cisplatin or carboplatin and gemcitabine included nausea, vomiting, hypothyroidism, constipation, diminished appetite, weight loss, cough, COVID-19 infection, lethargy, rash, and pyrexia.

The predominant adverse effects (≥20%) associated with single-agent penpulimab-kcqx were hypothyroidism and musculoskeletal discomfort. Fatal adverse responses were observed in 1% of patients, comprising one case each of pneumonitis, septic shock, colitis, and hepatitis.

The advised dosage of penpulimab-kcqx in conjunction with cisplatin or carboplatin and gemcitabine is 200 mg every three weeks until disease progression or intolerable toxicity, for a maximum duration of 24 months. The advised dosage of penpulimab-kcqx as a monotherapy for previously treated nasopharyngeal carcinoma is 200 mg biweekly until disease progression or intolerable toxicity, with a maximum duration of 24 months.