FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma

On April 23, 2025, the Food and Drug Administration approved penpulimab-kcqx (Akeso Biopharma Co., Ltd.) with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). FDA also approved penpulimab-kcqx as a single agent for adults with metastatic non-keratinizing NPC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

Full prescribing information for penpulimab-kcqx will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy of penpulimab-kcqx with cisplatin or carboplatin and gemcitabine was evaluated in Study AK105-304 (NCT04974398), a randomized, double-blind, multi-center trial in 291 patients with recurrent or metastatic NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients were randomized (1:1) to receive either penpulimab-kcqx with cisplatin or carboplatin and gemcitabine, followed by penpulimab-kcqx, or placebo with cisplatin or carboplatin and gemcitabine, followed by placebo. Chemotherapy regimens are described in the full prescribing information.

The primary efficacy outcome measure was progression-free survival (PFS), as assessed by a Blinded Independent Review Committee according to RECIST v1.1. Overall survival (OS) was a key secondary endpoint. Median PFS was 9.6 months (95% CI: 7.1, 12.5) in the penpulimab-kcqx arm and 7.0 months (95% CI: 6.9, 7.3) in the placebo arm (hazard ratio [HR] 0.45 [95% CI: 0.33, 0.62], two-sided p-value <0.0001), with 31% and 11% of patients alive and progression-free after 12 months of follow-up in the penpulimab-kcqx and placebo arms, respectively. While OS results were immature, with 70% of pre-specified deaths for the final analysis reported, no detrimental trend was observed.

Efficacy of single-agent penpulimab-kcqx was evaluated in Study AK105-202 (NCT03866967), an open-label, multicenter, single-arm trial conducted in a single country. The trial included a total of 125 patients with unresectable or metastatic non-keratinizing NPC who had disease progression after platinum-based chemotherapy and at least one other line of therapy. Patients received penpulimab-kcqx until disease progression or unacceptable toxicity, for a maximum of 24 months.

The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) according to RECIST v1.1 as assessed by an Independent Radiology Review Committee. The ORR was 28% (95% CI: 20, 37) and median DOR was not reached (95% CI: 9.2, not estimable).

Immune-mediated adverse reactions occurred with penpulimab-kcqx including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥20%) for penpulimab-kcqx with cisplatin or carboplatin and gemcitabine were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia. The most common adverse reactions (≥20%) for single-agent penpulimab-kcqx were hypothyroidism and musculoskeletal pain. Fatal adverse reactions occurred in 1% of patients, including a case each of pneumonitis, septic shock, colitis, and hepatitis.

The recommended penpulimab-kcqx dose with cisplatin or carboplatin and gemcitabine is 200 mg every three weeks until disease progression or unacceptable toxicity, for a maximum of 24 months. The recommended single-agent penpulimab-kcqx dose for previously treated NPC is 200 mg every two weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.

Expedited Programs

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted fast track designation, breakthrough designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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