FDA

Penpulimab approved for non-keratinizing nasopharyngeal carcinoma

April 29, 2025

Generic name: penpulimab-kcqx

Manufacturer: Akeso Biopharma

Approval date: April 23, 2025

FDA approved penpulimab-kcqx with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). The agency 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.

Efficacy

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 hadn’t 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.

The primary efficacy outcome measure was progression-free survival (PFS). 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% confidence interval [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). The ORR was 28% (95% CI, 20-37) and median DOR wasn’t reached (95% CI, 9.2, not estimable).

Safety

Immune-mediated adverse reactions reported with penpulimab-kcqx included 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.

Recommended dose

The recommended dosage of penpulimab-kcqx with cisplatin or carboplatin and gemcitabine is 200 mg q3wks until disease progression or unacceptable toxicity, for a maximum of 24 months. The recommended single-agent penpulimab-kcqx dosage for previously treated NPC is 200 mg q2wks until disease progression or unacceptable toxicity, for a maximum of 24 months.

Sources:

FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma

Penpulimab-kcqx [package insert]. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761258s000lbl.pdf Revised April 2025. Accessed April 28, 2025.