Penpulimab is a treatment option for cancer. It is a humanized monoclonal antibody, a laboratory-made protein that mimics the body’s own antibodies, developed to specifically combat cancer cells. This medication harnesses the power of the immune system.
Understanding Immunotherapy and Penpulimab’s Role
Immunotherapy is a cancer treatment approach that helps the body’s own immune system recognize and destroy cancer cells. Normally, T cells identify and attack abnormal cells, but cancer cells often evade detection. One common evasion strategy involves a protein called PD-1, found on T cells, which acts like a “brake” to prevent the immune system from overreacting. Cancer cells can express proteins called PD-L1 or PD-L2, which bind to PD-1 and effectively turn off the T cells, allowing the cancer to grow undetected.
Penpulimab is an anti-PD-1 IgG1 antibody, meaning it binds to the PD-1 receptor on T cells. By blocking the interaction between PD-1 and its ligands (PD-L1 and PD-L2), Penpulimab “releases the brakes” on the immune system. This reactivates the T cells, allowing them to recognize and attack cancer cells more effectively. Penpulimab’s unique Fc-null IgG1 antibody design is engineered to reduce unwanted immune-related side effects while maintaining strong anti-tumor activity. This design minimizes certain immune cell interactions, aiming for a more focused anti-cancer effect.
Clinical Efficacy Across Cancers
Penpulimab has demonstrated effectiveness in treating specific cancers, notably nasopharyngeal carcinoma (NPC) and hepatocellular carcinoma (HCC).
Nasopharyngeal Carcinoma (NPC)
The Phase 3 AK105-304 trial evaluated Penpulimab in combination with chemotherapy as a first-line treatment for recurrent or metastatic non-keratinizing NPC. Patients received Penpulimab with gemcitabine and cisplatin or carboplatin, followed by Penpulimab alone, or a placebo with chemotherapy.
The AK105-304 study reported a statistically significant improvement in progression-free survival (PFS). Median PFS was 9.6 months for the Penpulimab-chemotherapy group compared to 7.0 months for the placebo-chemotherapy group. This translates to a 45% reduction in the risk of disease progression or death. The objective response rate (ORR), which measures the percentage of patients whose tumors shrink or disappear, was 68.1% in the Penpulimab arm. While overall survival (OS) data were still maturing, no negative trends were observed at the time of analysis.
Penpulimab has also been evaluated as a single agent for metastatic non-keratinizing NPC that has progressed after platinum-based chemotherapy and at least one other prior treatment. The Phase 2 AK105-202 study, an open-label, single-arm trial, assessed Penpulimab in this setting. It reported an objective response rate (ORR) of 28%, with a median duration of response that had not yet been reached, indicating sustained benefits for some patients.
Hepatocellular Carcinoma (HCC)
In hepatocellular carcinoma (HCC), Penpulimab is being investigated in combination with other therapies. The Phase 3 ALTN-AK105-III-02 study explored Penpulimab with the multikinase inhibitor anlotinib for the first-line treatment of advanced HCC. This combination reduced the risk of disease progression or death by 47% compared to sorafenib, a standard first-line therapy. The median PFS for the Penpulimab-anlotinib group was 6.9 months, compared to 2.8 months for the sorafenib group.
The Penpulimab-anlotinib combination also reduced the risk of death by 31% in advanced HCC patients, with a median overall survival of 16.5 months versus 13.2 months for sorafenib. Biomarkers like PD-L1 expression and Epstein-Barr virus (EBV) DNA levels are considered in patient evaluation, particularly in NPC. Penpulimab’s benefits in NPC can extend across different PD-L1 levels and EBV DNA statuses.
Managing Side Effects
Like all medications, Penpulimab can cause side effects, particularly immune-related adverse events (irAEs). These occur when the reactivated immune system also targets healthy tissues. Common irAEs reported in clinical trials include fatigue, nausea, decreased appetite, and skin rashes. Patients may also experience symptoms like cough, fever, diarrhea, or constipation.
More serious, though less frequent, immune-mediated reactions can affect various organs. These may include pneumonitis (lung inflammation), colitis (colon inflammation), hepatitis (liver inflammation), and endocrinopathies (disorders of hormone-producing glands). While these events can be serious, they are generally manageable with appropriate medical intervention, often involving corticosteroids or other immunosuppressive drugs.
Regulatory Approvals and Ongoing Research
Penpulimab has received regulatory approvals in various regions for different cancer types.
China Approvals
- Approved in August 2021 for adults with relapsed or refractory classic Hodgkin lymphoma.
- Approved in January 2023 for first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer in combination with chemotherapy.
- Approved for first-line and third-line or later treatment for metastatic nasopharyngeal carcinoma.
United States Approvals
- Approved in April 2025 for first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma, in combination with cisplatin or carboplatin and gemcitabine.
- Approved as a single agent for adults with metastatic non-keratinizing NPC who experienced disease progression after platinum-based chemotherapy and at least one other prior line of therapy.
Ongoing research continues to explore Penpulimab’s potential in other indications and in combination with different therapies, such as the ongoing Phase 3 trial combining it with anlotinib for hepatocellular carcinoma.