FDA Approves 2 Indications for Penpulimab-kcqx in Non-Keratinizing NPC

Fatal AEs occurred in 1% of patients and included 1 case each of pneumonitis, septic shock, colitis, and hepatitis.

On April 23, FDA approved penpulimab-kcqx with cisplatin or carboplatin and gemcitabine for the frontline treatment of adult patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC), in addition to approving penpulimab-kcqx monotherapy for adults with metastatic non-keratinizing NPC whose disease has progressed on or after platinum-based chemotherapy and one or more previous lines of therapy.¹

Combination Therapy Efficacy

The efficacy of the former approval was assessed in the randomized, double-blind, multicenter trial Study AK105-304 (NCT04974398), in which 291 patients with recurrent/metastatic NPC who had not received prior systemic chemotherapy were evaluated.

Patients were randomized 1:1 to receive treatment with either penpulimab-kcqx with cisplatin or carboplatin and gemcitabine preceding penpulimab-kcqx, or placebo with cisplatin or carboplatin and gemcitabine preceding placebo.

The primary end point was progression-free survival (PFS) according to RECIST v1.1 criteria. Median PFS in the penpulimab-kcqx arm was 9.6 months (95% CI, 7.1-12.5), compared with 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 < .0001). After 12 months of follow-up, 31% and 11% of patients in respective arms were alive and progression-free.

Overall survival (OS) was a secondary end point; OS data were immature at the time of analysis. However, 70% of pre-specified deaths for the final analysis were reported with no detrimental trend observed.

Single-Agent Therapy Efficacy

The efficacy of penpulimab-kcqx was determined in the open-label, multicenter, single-arm Study AK105-202 (NCT03866967) trial, which was conducted in China.² The trial assessed 125 patients with unresectable or metastatic non-keratinizing NPC whose disease progressed after platinum-based chemotherapy and one or more other lines of therapy.

Patients received penpulimab-kcqx until they experienced disease progression or unacceptable toxicity for a maximum of 24 months. The primary end points were duration of response (DOR) as evaluated by RECIST v1.1 and objective response rate (ORR) and.

Median DOR was not reached (95% CI, 9.2-not estimable), and ORR was 28% (95% CI, 20-37).

Adverse Events

Several immune-mediated adverse events (AEs) were observed with penpulimab-kcqx, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.

The most frequent AEs, which occurred in at least 20% of patients receiving penpulimab-kcqx with cisplatin or carboplatin and gemcitabine were nausea, emesis, hypothyroidism, constipation, decreased appetite, weight loss, cough, COVID-19 infection, fatigue, rash, and fever.

In single-agent penpulimab-kcqx, the most common AEs, occurring in at least 20% of patients, were hypothyroidism and musculoskeletal pain. Fatal AEs, including 1 case each of pneumonitis, septic shock, colitis, and hepatitis, occurred in 1% of patients.

Dosing Information

For combination therapy, the FDA recommends 200 mg of penpulimab-kcqx every 3 weeks. Monotherapy is recommended at 200 mg every 2 weeks. Treatment with penpulimab-kcqx should be discontinued in the case of disease progression or unacceptable toxicity.

Reference

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 anti-PD-1 AK105 in patients with metastatic nasopharyngeal carcinoma. Clinicaltrials.gov. March 3, 2007. Updated February 27, 2025. Accessed April 24, 2025. https://clinicaltrials.gov/study/NCT03866967?id=NCT03866967&rank=1