Penpulimab

Last updated

Penpulimab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target PD-1
Clinical data
Other namesAK105, penpulimab-kcqx
License data
Routes of
administration 		Intravenous
Drug class Antineoplastic agent
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
PubChem SID
IUPHAR/BPS
DrugBank
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C6434H9922N1718O2012S46
Molar mass 145008.92 g·mol−1

Penpulimab is a humanized monoclonal antibody used for the treatment of cancer. [1] It targets the programmed cell death protein 1 (PD-1) receptor. [1] [2]

Contents

Penpulimab was approved for medical use in China in August 2021, [3] and in the United States in April 2025. [4]

Medical uses

In the United States, penpulimab is indicated for the treatment of non-keratinizing nasopharyngeal carcinoma. [1] [4]

In August 2021, penpulimab received its first approval in China for the treatment of adults with relapsed or refractory classic Hodgkin lymphoma who have undergone at least second-line chemotherapy. [3]

In January 2023, the National Medical Products Administration of China approved penpulimab in combination with chemotherapy for the first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer. [5]

Adverse effects

The most common adverse effects associated with penpulimab include:

Pharmacology

Mechanism of action

Penpulimab binds to the PD-1 receptor on T cells, preventing interaction with its ligands, PD-L1 and PD-L2. [6] This blockade restores T-cell-mediated immune responses against tumor cells. The antibody has been engineered with modifications to its Fc region to eliminate Fcγ receptor binding and Fc-mediated effector functions, reducing the risk of immune-related adverse effects such as antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis. [7]

Penpulimab demonstrates a slower dissociation rate from the PD-1 receptor compared to other PD-1 inhibitors, resulting in higher receptor occupancy and enhanced T-cell activity. [6] This property is attributed to its unique binding interactions with the glycosylated N58 residue on the BC loop of the PD-1 receptor. [6]

Manufacturing

Penpulimab is produced using recombinant DNA technology in Chinese hamster ovary cells. It has been designed with an IgG1 backbone and modified Fc regions to minimize immune-related side effects. [7]

History

The efficacy of penpulimab with cisplatin or carboplatin and gemcitabine was evaluated in study AK105-304 (NCT04974398), a randomized, double-blind, multi-center trial in 291 participants with recurrent or metastatic nasopharyngeal carcinoma who had not received previous systemic chemotherapy for recurrent or metastatic disease. [4] Participants were randomized (1:1) to receive either penpulimab with cisplatin or carboplatin and gemcitabine, followed by penpulimab, or placebo with cisplatin or carboplatin and gemcitabine, followed by placebo. [4]

The efficacy of single-agent penpulimab was evaluated in study AK105-202 (NCT03866967), an open-label, multi-center, single-arm trial conducted in a single country. [4] The trial included a total of 125 participants with unresectable or metastatic non-keratinizing nasopharyngeal carcinoma who had disease progression after platinum-based chemotherapy and at least one other line of therapy. [4] Participants received penpulimab until disease progression or unacceptable toxicity, for a maximum of 24 months. [4]

Society and culture

In March 2025, penpulimab, was approved by the National Medical Products Administration in China for the first-line treatment of recurrent or metastatic nasopharyngeal cancer in combination with chemotherapy. [8]

In April 2025, the US Food and Drug Administration (FDA) approved penpulimab-kcqx with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma. [4] The FDA also approved penpulimab-kcqx as a single agent for adults with metastatic non-keratinizing nasopharyngeal carcinoma with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. [4] The FDA granted the application for penpulimab fast track, breakthrough therapy, and orphan drug designations. [4]

Names

Penpulimab is the international nonproprietary name. [9]

Penpulimab is sold under the brand name 安尼可 (Anike) in China. [3]

Research

Penpulimab is being studied in various clinical trials to evaluate its efficacy and safety for additional cancer indications, including nasopharyngeal carcinoma, [10] [11] non-small-cell lung cancer, and other solid tumors. [3]

References

  1. 1 2 3 4 fda.gov
  2. ↑ "Penpulimab - Akeso Biopharma/Chia Tai Tianqing Pharmaceutical Group". AdisInsight. Springer Nature Switzerland AG.
  3. 1 2 3 4 Dhillon S (December 2021). "Penpulimab: First Approval". Drugs. 81 (18): 2159–2166. doi:10.1007/s40265-021-01640-9. PMID   34813051.
  4. 1 2 3 4 5 6 7 8 9 10 "FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma". U.S. Food and Drug Administration (FDA). 23 April 2025. Archived from the original on 24 April 2025. Retrieved 24 April 2025.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. ↑ "China NMPA Approved Penpulimab for First-line Treatment of Locally Advanced or Metastatic Squamous NSCLC". Akeso (Press release).
  6. 1 2 3 4 5 Song Y, Zhou K, Jin C, Qian Z, Hou M, Fan L, et al. (2021). "A phase II study of penpulimab, an anti-PD-1 antibody, in patients with relapsed or refractoryclassic Hodgkin lymphoma (cHL)". Journal of Clinical Oncology. 39 (15): abstr 7529. doi:10.1200/JCO.2021.39.15_suppl.7529.
  7. 1 2 "The only new PD-1 monoclonal antibody that applies the IgG1 subtype with modified Fc domain". Akeso. 2021.
  8. ↑ "Akeso's Penpulimab Receives NMPA Approval for First-Line Treatment of Nasopharyngeal Cancer". Akeso (Press release). 17 March 2025. Retrieved 24 April 2025.
  9. ↑ World Health Organization (2021). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85". WHO Drug Information. 35 (1). hdl: 10665/340684 .
  10. ↑ Liu X, Shen H, Zhang L, Huang W, Zhang S, Zhang B (May 2024). "Immunotherapy for recurrent or metastatic nasopharyngeal carcinoma". npj Precision Oncology. 8 (1): 101. doi:10.1038/s41698-024-00601-1. PMC   11099100 . PMID   38755255.
  11. ↑ Dai Z, Li N, Wang J, Tan C, Zhang Y, Liu L (2023). "Anti-PD-1/PD-L1 for nasopharyngeal carcinoma: a comprehensive analysis of registered trials on ClinicalTrials.gov". Frontiers in Pharmacology. 14: 1212813. doi: 10.3389/fphar.2023.1212813 . PMC   10679443 . PMID   38026930.

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