Penpulimab Immunotherapy Receives FDA Approval for Nasopharyngeal Cancer

On 23 April 2025, the US Food and Drug Administration (FDA) approved penpulimab-kcqx (Akeso Biopharma Co., Ltd.) with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic nonkeratinizing nasopharyngeal cancer.

Penpulimab-kcqx was also approved as a single agent for metastatic nonkeratinizing nasopharyngeal cancer in patients whose disease had progressed after platinum-based chemotherapy and who had received at least one additional line of treatment.

Penpulimab: Mechanism of Action and Drug Characteristics

Penpulimab is a humanized, Fc-engineered IgG1 monoclonal antibody belonging to the immune checkpoint inhibitor class. Its target, PD-1 (Programmed Cell Death Protein-1), is a critical checkpoint that prevents immune cells from becoming active against tumor cells. Penpulimab blocks interactions between PD-1 and PD-L1 and PD-L2, enabling the immune system to reactivate against the tumor.

Penpulimab was first approved in August 2021 by China's National Medical Products Administration (NMPA) for patients with relapsed or refractory classical Hodgkin lymphoma who had received at least two lines of chemotherapy. This approval took place in China, the first country to make penpulimab available for clinical use.

In January 2023, it was subsequently approved in China as first-line treatment with chemotherapy for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). In March 2025, it also received first-line approval in China for recurrent or metastatic nasopharyngeal cancer.

Efficacy Demonstrated in Clinical Trials

The efficacy of penpulimab was confirmed in two important clinical trials:

AK105-304 Trial:

• In this study of 291 patients, median progression-free survival (PFS) reached 9.6 months with the penpulimab-kcqx combination, compared with 7.0 months in the control group.

• At 12 months of follow-up, 31% of patients in the penpulimab group were alive and disease-free, compared with 11% in the placebo group.

• The risk of disease progression decreased by 55%.

AK105-202 Trial:

• In this study of 125 previously treated patients, single-agent penpulimab produced an objective response rate (ORR) of 28%, and responses lasted so long that a median duration could not be established.

The First Immune Checkpoint Inhibitor Previously Approved by the FDA: Toripalimab

In nasopharyngeal cancer immunotherapy, the first FDA approval was granted on 27 October 2023 to toripalimab-tpzi (Loqtorzi). Toripalimab, also a PD-1-targeting immune checkpoint inhibitor, was approved with cisplatin and gemcitabine as first-line treatment, and as a single agent for nasopharyngeal cancer progressing after platinum-based treatment.

The efficacy of toripalimab had also been established in two important trials:

• In JUPITER-02, the toripalimab-chemotherapy combination significantly improved progression-free survival.

• In POLARIS-02, previously treated patients had an objective response rate of 21% and a median response duration of 14.9 months.

Side Effects and Safety Profile

Important penpulimab side effects include immune-mediated reactions, such as pneumonitis, colitis, hepatitis, endocrine disorders, nephritis and skin reactions. Nausea, vomiting, hypothyroidism, weight loss and fatigue were observed with combination treatment, while hypothyroidism and musculoskeletal pain were most commonly reported with single-agent use.

Conclusion and Clinical Significance

The FDA approvals of penpulimab-kcqx and toripalimab are regarded as the beginning of an immunotherapy era in nasopharyngeal cancer treatment. By broadening treatment options, these developments offer substantial hope to clinicians and patients.