Camrelizumab
Overview
Camrelizumab is a humanized anti-PD-1 monoclonal antibody immune checkpoint inhibitor developed by Jiangsu Hengrui Pharmaceuticals of China. Its development code name is SHR-1210, and its trade name in China is AiRuiKa (艾瑞卡, AiRuiKa). After receiving its first approval from China's National Medical Products Administration (NMPA) in 2019, it has expanded its indications to include Hodgkin lymphoma, hepatocellular carcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, non-small cell lung cancer, and others. It is among the most widely used PD-1 inhibitors developed in China, and it has attracted attention in global clinical settings due to its low price and active combination therapy research.
Main Content
Mechanism of Action
Camrelizumab selectively binds to the PD-1 receptor on the surface of T cells, blocking its interaction with PD-L1/PD-L2 expressed by tumor cells. As a result, PD-1-mediated inhibitory signaling is released, activation and proliferation of tumor-specific T cells are restored, and immune evasion mechanisms in the tumor microenvironment are weakened. Its backbone is of the IgG4 isotype and is designed to minimize Fc-mediated effector function.
Development History
- Around 2012: Hengrui Pharmaceuticals began development as SHR-1210
- May 2019: Approved by China's NMPA for relapsed/refractory classic Hodgkin lymphoma (cHL) (the first approved domestic Chinese PD-1 inhibitor)
- 2020: Added indications for second-line treatment of hepatocellular carcinoma, esophageal squamous cell carcinoma, etc.
- After 2021: Expanded to nasopharyngeal carcinoma, non-small cell lung cancer, cervical cancer, etc.
- 2023: Entered a licensing agreement with global partner Elevar Therapeutics for a hepatocellular carcinoma combination therapy
- May 2024: U.S. FDA issued a Complete Response Letter (CRL) for the hepatocellular carcinoma combination therapy marketing application (mainly manufacturing/facility-related issues)
Major Indications
1. Relapsed/refractory classic Hodgkin lymphoma: Approved based on a high objective response rate in patients who relapsed after second-line or later treatment.
2. Advanced hepatocellular carcinoma: Monotherapy or combination therapy for patients who failed prior treatment.
3. Esophageal squamous cell carcinoma: Combination with chemotherapy in first- and second-line treatment settings.
4. Nasopharyngeal carcinoma: Improvement in progression-free survival has been reported when combined with chemotherapy in recurrent/metastatic nasopharyngeal carcinoma.
5. Non-small cell lung cancer, cervical cancer, gastric cancer, etc.: Clinical development has proceeded as monotherapy or combination therapy.
Adverse Reactions and Safety
The most characteristic adverse reaction is reactive cutaneous capillary endothelial proliferation (RCCEP). It appears as red nodular hemangiomatous lesions on the skin, and it is reported at an especially high frequency with camrelizumab (60-80% depending on the study), while it is rare with other PD-1 inhibitors. It is usually mild and tends to resolve spontaneously, but attention is needed due to cosmetic issues and bleeding risk. In addition, immune-related adverse reactions (thyroid dysfunction, hepatotoxicity, pneumonitis, skin rash, etc.), infusion-related reactions, and myelosuppression are commonly seen when combined with chemotherapy.
Combination Therapy
A key strategy for camrelizumab is combination with the VEGFR2 inhibitor apatinib (rivoceranib). This approach combines immune checkpoint inhibition and anti-angiogenesis inhibition to improve the tumor microenvironment, and in the phase 3 hepatocellular carcinoma trial (CARES-310), camrelizumab + rivoceranib significantly prolonged overall survival compared with sorafenib. In addition, triple combinations with chemotherapy, radiotherapy, and other targeted therapies are being actively studied.
Latest Trends
As of 2024-2025, the biggest issue is regulatory entry into the United States and Europe. For the first-line combination therapy for hepatocellular carcinoma, FDA issued a Complete Response Letter in May 2024, delaying approval, but manufacturing facility and quality control remediation work is ongoing, and resubmission and re-review are being discussed. At the same time, within China, clinical trials are expanding into neoadjuvant/adjuvant settings along with expansion of surrounding indications such as nasopharyngeal and esophageal cancer. In addition, as price competition in the PD-1 inhibitor market intensifies, camrelizumab's low-price strategy and expanded access in developing countries are being highlighted, and in Korea it is still mainly used for clinical trials and research purposes without formal approval. Elucidating the mechanism of immune-related adverse reactions, especially RCCEP, and establishing management guidelines remain major research topics.
Related Topics
- [[Immune checkpoint inhibitor]]
- [[PD-1]]
- [[Hepatocellular carcinoma]]
- [[Apatinib]]
- [[Antibody drug]]
- [[Hengrui Pharmaceuticals]]