On October 24, 2022, the official website of AstraZeneca (AstraZeneca) announced that the new indication of the anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) full humanized monoclonal antibody Tremelimumab (Tremelimumab) has been approved by the US FDA and combined with PD-L1 monoclonal antibody Duvalizumab (Imfinzi) is used to treat patients with unresectable hepatocellular carcinoma (HCC). This provides new immune combination therapy , which consists of dual immune checkpoint inhibitors, for patients with liver cancer.
Trimemuzumab is a fully humanized monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4) that blocks the signaling pathway that helps tumors escape immune examination. Trimemuzumab stimulates the body's immune system to attack tumor cells by binding to CTLA-4 protein expressed on the surface of activated T lymphocytes .
Trade name: Imjudo
Generic name: Tremelimumab (Tremelimumab/Teximumab)
Target: CTLA-4
First approved in the United States: October
October 
022
11 3 China's first approval: not approved
approved indication: liver cancer
Recommended dose: body weight Patients with ≥30kg: received 300 mg of trimemuzumab combined with 1500 mg of valizumab on the first day of the first cycle, followed by continuous treatment with 1500 mg of valizumab every 4 weeks; patients with body weight <30kg:>
valizumab is a selective, high-affinity human IgG1 monoclonal antibody that blocks the binding of programmed cell death ligand 1 (PD-L1) with programmed death receptor 1 (PD-1) and CD-80. stimulates anti-tumor T cell activity .
Trade name: Imfinzi (Yingfeifan)
Generic name: durvalumab (Dvaluzumab, Duvaluzumab)
Target: PD-L1
First approved in the United States : May 2017
China's first approval: December 2019
Approved Indications: Urothelial cancer, Non-small cell lung cancer (China), Small cell lung cancer (China), Biliary cancer , liver cancer
Specifications: 500 mg/10mL or 120 mg/2.4mL
Recommended dose: Patients with weight ≥30kg: receive 300mg trimemuzumab combined with 1500mg valizumab on the first day of the first cycle, followed by continuous treatment with 1500mg valizumab monotherapy every 4 weeks; patients with weight <30kg:>
Give medicine plan: Low-income patients: first buy 2 and get 2, then buy 4 and get 4, then buy 6 and get 8; minimum living security patients: free until the disease progresses.
Storage conditions: °C~8°C Refrigerated and save
Picture Note: The domestically listed immunosuppressant summary (because WeChat automatically compresses pictures, please add to add medical operations to obtain )
Picture Note: A summary of global marketed immunosuppressants (because WeChat automatically compresses pictures, please add to add medical operations to obtain )
clinical data
This approval is based on the results of a global, multi-center, randomized, open-label Phase III HIMALAYA study.This trial mainly evaluates the efficacy and safety of trimemuzumab combined with valizumab regimen compared with valizumab and sorafinib monotherapy in patients with unresectable HCC. These patients have not received systematic treatment before and are not subject to local treatment . The population characteristics of the enrolled patients include: median age was 65 years old; 46% of patients were white, 49% of patients were Asian; 99% of patients had Child-Pugh grade A; 26% of patients had large blood vessel invasion and 53% of patients had extrahepatic spread; viral pathogenesis: hepatitis B (31%), hepatitis C (27%) and uninfected (42%).
The main endpoint of this trial is overall survival (OS); secondary endpoint includes time to progress (TTP), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and duration of response (DOR).
trial results showed that the median OS of the tramemuzumab combined with valiumab (n=393) group VS sorafenib (n=389) group was 6.4 months VS 13.8 months ; the median PFS was 3.8 months VS 4.1 months; the ORR was 0.1% VS 5.1% , and the partial response rate (PR) was 7.0% VS 5.1% ; the median DOR was 2.3 months VS 18.4 months , the DOR rate for ≥6 months was 82.3% VS 78.9% , and the DOR rate for ≥12 months was 65.8% VS 63.2% .
Figure Note: Clinical data on first-line treatment of liver cancer with quamemuzumab combined with quamemuzumab
Adverse reactions
In the HIMALAYA trial, the most common adverse reactions of any grade in the quamemuzumab combined with quamemuzumab include: rash (32%), diarrhea (27%), fatigue (26%), skin itching (23%), musculoskeletal pain (22%), abdominal pain (20%), poor appetite (17%), hypothyroidism (14%), fever (13%), nausea (12%), insomnia (10%).
The most common grade 3-4 adverse reactions include: diarrhea (6%), fatigue (3.9%), rash (2.8%), musculoskeletal pain (2.6%), abdominal pain (1.8%), poor appetite (1.3%), fever (0.3%), insomnia (0.3%).
Figure Note: Adverse reactions of tramemuzumab combined with valiumumab for first-line treatment of liver cancer
The most common laboratory abnormal data of any level in the tramemuzumab combined with valiumumab group include: aspartate aminotransferase elevated (63%), alanine aminotransferase elevated (56%), hemoglobin reduction (52%), hemoglobin reduction (52%), 1 hyponatremia (46%), bilirubin increased (41%), alkaline phosphatase increased (41%), lymphocyte decreased (41%), glucose levels increased (39%), blood calcium decreased (34%), albumin decreased (31%), thrombocytopenia (29%), hyperkalemia (28%), creatinine increased (21%), and leukocyte decreased (20%).
The most common 3-4 laboratory abnormal data include: aspartate aminotransferase elevation (27%), alanine aminotransferase elevation (18%), hyponatremia (15%), hrefoma (15%), ht The level of ml1 glucose was increased (14%), lymphocytes decreased (11%), bilirubin increased (8%), alkaline phosphatase decreased (8%), hemoglobin decreased (4.8%), hyperkalemia (3.8%), thrombocytopenia decreased (1.6%), creatinine increased (1.3%), leukocyte decreased (0.8%) albumin decreased (0.5%).
Figure Note: Laboratory abnormal data for the treatment of liver cancer with tramemuzumab combined with valiumumab for the first-line treatment of liver cancer
Warnings and precautions
Immune-mediated pneumonia
Immune-mediated colitis
Immune-mediated colitis
Immune-mediated hepatitis
Immune-mediated endocrine disease
Immune-mediated nephritis with renal dysfunction
Immune-mediated skin reaction
Immune-mediated pancreatitis
Other immune-mediated adverse reactions
infusion-related reactions
degree complications of allogeneic hematopoietic stem cell transplantation after valiumumab
Embryonic toxicity
Reference source:
https://den8dhaj6zs0e.cloudfront.net
https://www.astrazeneca.com
https://www.fda.gov
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