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The US Food and Drug Administration (FDA) has approved penpulimab-kcqx (Akeso Biopharma) in combination with cisplatin or carboplatin and gemcitabine as first-line treatment for adults with certain types of nasopharyngeal carcinoma (NPC), and as a single agent for certain patients with NPC disease progression on or after other treatments.

Specifically, the novel programmed death 1 monoclonal antibody was approved for first-line treatment, along with platinum-based chemotherapy for those with recurrent of metastatic non-keratinizing NPC, and as a single agent for those with metastatic disease that progresses on or after platinum-based chemotherapy and at least one other prior line of therapy, according to an FDA press release.

Approval in the first-line setting was based on efficacy and safety demonstrated in the randomized, phase 3 AK105-304 study of 291 patients with recurrent or metastatic NPC who had not received systemic chemotherapy for their 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. 

Median progression-free survival, the primary efficacy outcome measure, was 9.6 vs 7.0 months in the treatment vs placebo group (hazard ratio [HR], 0.45). After 12 months of follow-up, 31% and 11% of patients in the arms, respectively, were alive and progression free.

Results for overall survival, a key secondary endpoint, were not mature, but “no detrimental trend was observed,” the FDA noted.

Approval for single-agent penpulimab-kcqx after chemotherapy and at least one other prior line of therapy was based on findings from the pivotal open-label, single-arm AK105-202 Study 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. 

The AK105-202 study supported the two Biologics License Applications for the agent, according to an Akeso press release, which notes that “[p]reviously, the FDA granted penpulimab-kcqx Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation for the NPC indications, highlighting the crucial unmet need for this therapy.”

Patients in the study received penpulimab-kcqx until disease progression or unacceptable toxicity, for up to 24 months.

The objective response rate was 28% and the median duration of response was not reached. 

Immune-mediated adverse reactions occurred with penpulimab-kcqx, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions. Adverse reactions occurring in at least 20% of patients receiving 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. 

Adverse reactions occurring in at least 20% of patients receiving single-agent penpulimab-kcqx were hypothyroidism and musculoskeletal pain. Fatal adverse reactions occurred in 1% of patients, including one case each of pneumonitis, septic shock, colitis, and hepatitis. 

Study results will be presented at the 2025 American Association for Cancer Research Annual Meeting, Akeso noted in the press release. 

“According to the WHO 2020 Global Cancer Statistics, over 133,000 new NPC cases are diagnosed annually worldwide, with more than 70% of the patients presenting with locally advanced disease,” the company stated. “Recurrent or metastatic NPC has a poor prognosis and limited survival. Penpulimab-kcqx's FDA approval will expand the number of NPC patients that can benefit from its treatment.” 

The recommended penpulimab-kcqx dose with cisplatin or carboplatin and gemcitabine is 200 mg every 3 weeks until disease progression or unacceptable toxicity, for up to 24 months. With single agent penpulimab-kcqx for this indication, the recommended dose is 200 mg every 2 weeks until disease progression or unacceptable toxicity, for up to 24 months. 

Penpulimab has been approved in China for multiple indications, including as a first-line treatment along with chemotherapy for locally advanced or metastatic squamous non-small cell lung cancer, third-line treatment of relapsed or refractory classical Hodgkin’s lymphoma, and third-line treatment of recurrent or metastatic NPC. Late-stage clinical trial are progressing for liver cancer, gastric cancer, and other indications, according to Akeso product information.

Full prescribing information for penpulimab-kcqx is available on Drugs@FDA.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.comor on X: @SW_MedReporter.