FDA Approves Penpulimab for Non-Keratinizing Nasopharyngeal Carcinoma

FDA

The FDA has approved penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine for the first-line treatment of adult patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC); and as a single agent for adult patients with metastatic non-keratinizing NPC with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy.

The regulatory approval of the combination made on April 23, 2025, was supported by data from the phase 3 Study AK105-304 (NCT049743980). Single-agent penpulimab was approved based on findings from the phase 2 Study AK105-202 (NCT03866967).

Findings from Study AK105-304 showed that patients treated with penpulimab plus chemotherapy achieved a median progression-free survival (PFS) of 9.6 months (95% CI, 7.1-12.5) vs 7.0 months (95% CI, 6.9-7.3) in those given placebo plus chemotherapy (HR, 0.45; 95% CI, 0.33-0.62; 2-sided P < .0001).

In Study AK105-202, data demostrated that patients treated with single-agent penpulimab achieved an overall response rate (ORR) of 28% (95% CI, 20%-37%). The median duration of response (DOR) was not reached (95% CI, 9.2-not estimable).

Study AK105-304 Overview

The randomized, double-blind, multicenter trial enrolled patients 18 to 75 years of age with histologically or cytologically confirmed recurrent or metastatic NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease.1,2 Key inclusion criteria consisted of an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; at least 1 measurable lesion per RECIST 1.1 criteria; and adequate organ function.2

Patients were randomly assigned in a 1:1 fashion to receive penpulimab in combination with cisplatin or carboplatin and gemcitabine, followed by penpulimab alone; or placebo with cisplatin or carboplatin and gemcitabine, followed by placebo.1

PFS served as the trial's primary end points. Secondary end points included overall survival (OS), ORR, DOR, disease control rate, and safety.2

Study AK105-202 Background

The multicenter, single-arm, open-label, phase 2 study included patients 18 to 75 years of age with histologically confirmed unresectable or metastatic non-keratinizing NPC who had disease progression after platinum-based chemotherapy and at least one other line of therapy.1,3 Patients needed to have at least 1 measurable tumor lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ function.3

All patients received penpulimab until disease progression or unacceptable toxicity for up to 24 months.1

ORR served as the trial's primary end point. Secondary end points included PFS, DOR, DCR, OS, and safety.

Penpulimab Safety Overview

The most common adverse effects (AEs) reported in at least 20% of patients treated with penpulimab in combination with cisplatin or carboplatin and gemcitabine included nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia.

Among patients receiving single-agent penpulimab, the most common AEs that occurred in at least 20% of patients comprised hypothyroidism and musculoskeletal pain. Fatal AEs reactions occurred in 1% of patients, including pneumonitis, septic shock, colitis, and hepatitis (n = 1 each).

The recommended dose of penpulimab in the combination is 200 mg once every 3 weeks until disease progression or unacceptable toxicity for a maximum of 24 months. Single-agent penpulimab is recommended at 200 mg every 2 weeks until disease progression or unacceptable toxicity for a maximum of 24 months.

References

1. FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma. FDA. April 23, 2025. Accessed April 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma
2. A study of penpulimab (AK105) in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma. ClinicalTrials.gov. Updated April 13, 2025. Accessed April 24, 2025. https://clinicaltrials.gov/study/NCT04974398
3. A study of anti-PD-1 AK105 in patients with metastatic nasopharyngeal carcinoma. ClinicalTrials.gov. Updated February 27, 2025. Accessed April 24, 2025. https://clinicaltrials.gov/study/NCT03866967