FDA Approves Penpulimab-Kcqx for Nasopharyngeal Carcinoma

On April 23, 2025, the Food and Drug Administration (FDA) granted approval to Akeso Biopharma Co., Ltd. for its drug penpulimab-kcqx. This approval covers its use in combination with cisplatin or carboplatin and gemcitabine for the initial treatment of adult patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). Additionally, penpulimab-kcqx can now be used as a stand-alone treatment for adults with metastatic non-keratinizing NPC who have experienced disease progression following platinum-based chemotherapy and at least one other previous therapy.

The effectiveness and safety of penpulimab-kcqx were proven through two key clinical trials: Study AK105-304 and Study AK105-202. Study AK105-304 was a randomized, double-blind, multi-center trial involving 291 patients who had recurrent or metastatic NPC yet had not previously undergone systemic chemotherapy for their condition. Participants were divided equally to receive either penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine, or a placebo combined with the same chemotherapy regimen. The primary goal was to measure progression-free survival (PFS), which was determined by a Blinded Independent Review Committee using RECIST v1.1 criteria.

The results indicated a median PFS of 9.6 months for those treated with penpulimab-kcqx, compared to 7.0 months for the placebo group. This represented a hazard ratio of 0.45, with a two-sided p-value of less than 0.0001. After a year, 31% of patients in the penpulimab-kcqx group remained alive without disease progression, compared to 11% in the placebo group. Although overall survival data was not fully mature, no negative trends were observed, with 70% of predetermined deaths at the time of the interim analysis.

The second trial, Study AK105-202, was an open-label, multicenter, single-arm trial conducted in one country. It involved 125 patients with unresectable or metastatic non-keratinizing NPC who had experienced disease progression following platinum-based chemotherapy and another line of therapy. Participants received penpulimab-kcqx until either disease progression or unacceptable toxicity occurred, for a maximum of 24 months. The study's main objectives were to measure the objective response rate (ORR) and duration of response (DOR) according to RECIST v1.1 criteria, as assessed by an Independent Radiology Review Committee. The results showed an ORR of 28%, with the median DOR not yet reached at the time of evaluation.

In terms of safety, penpulimab-kcqx was associated with immune-mediated adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin reactions. For those treated with penpulimab-kcqx alongside chemotherapy, common adverse reactions (occurring in 20% or more of patients) included nausea, vomiting, hypothyroidism, constipation, decreased appetite and weight, cough, COVID-19 infection, fatigue, rash, and fever. When used as a single agent, common adverse reactions included hypothyroidism and musculoskeletal pain. Fatal adverse reactions were reported in 1% of patients, with individual cases of pneumonitis, septic shock, colitis, and hepatitis.

For patients receiving penpulimab-kcqx with cisplatin or carboplatin and gemcitabine, the recommended dosage is 200 mg every three weeks, continuing until disease progression or unacceptable side effects for up to 24 months. When administered as a single agent for previously treated NPC, the recommended dose is 200 mg every two weeks, similarly continued until disease progression or unacceptable side effects for a maximum duration of 24 months.

This FDA approval process benefited from the Assessment Aid, a voluntary submission designed to streamline the FDA's evaluation. The application received fast track, breakthrough, and orphan drug designations, underscoring its significance in the treatment of this serious condition.