In short
Cadonilimab (AK104) is an investigational bispecific antibody that targets two immune checkpoints at once: PD-1 and CTLA-4. It is being studied in a Phase 2 trial with 120 participants for advanced hepatocellular carcinoma (HCC), the most common form of liver cancer, in people whose disease has worsened after previous treatment. The trial compares cadonilimab plus lenvatinib against lenvatinib alone.
Key points
- Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, two immune checkpoints.
- One registered EU trial is Phase 2, with 120 participants planned.
- The condition studied is advanced hepatocellular carcinoma (liver cancer).
- Participants must have progressed on atezolizumab and bevacizumab before joining.
- The main outcome is objective response rate (ORR) per RECIST v1.1, assessed by blinded independent central review.
- The trial is currently authorised but not yet recruiting.
What is cadonilimab?
Cadonilimab, also known by its development code AK104, is a bispecific antibody. A bispecific antibody is a protein-based medicine designed to attach to two different targets at the same time. Cadonilimab binds to two immune checkpoint proteins: programmed cell death-1 (PD-1) and CTLA-4. It is an investigational substance, meaning it has not yet received marketing authorisation as a medicine in the European Union or the United States.
How does cadonilimab work?
PD-1 and CTLA-4 are proteins on immune cells called T cells. Cancer cells can use these proteins to switch off the immune response, which helps the tumour grow. By blocking both PD-1 and CTLA-4 at once, cadonilimab is designed to release the brakes on the immune system so that T cells can recognise and attack cancer cells more effectively. This dual targeting is the reason cadonilimab is described as a bispecific antibody.
Which conditions is cadonilimab being studied for?
- Advanced hepatocellular carcinoma (HCC) — the most common type of primary liver cancer. The registered trial includes people whose disease has worsened after treatment with atezolizumab and bevacizumab.
- Locally advanced gastric or gastro-oesophageal junction adenocarcinoma — a type of stomach cancer. A study protocol describes cadonilimab combined with chemotherapy as neoadjuvant treatment, meaning treatment given before surgery.
How is cadonilimab given?
In the registered trial, cadonilimab is given as an intravenous infusion, meaning it is delivered directly into a vein. The dose reported in the trial record is 6 mg per kilogram of body weight. Lenvatinib, the comparison medicine in the same trial, is given as 12 mg hard capsules taken by mouth.
What do the clinical trials show?
One EU clinical trial is registered for cadonilimab in advanced hepatocellular carcinoma. It is a Phase 2 interventional study planning to enrol 120 participants. The trial is currently authorised, which means it has received regulatory approval to proceed but is not yet recruiting. Participants are people with advanced HCC whose disease has progressed on atezolizumab and bevacizumab. The trial compares cadonilimab plus lenvatinib against lenvatinib alone.
The main outcome measured is the objective response rate (ORR), which is the proportion of participants whose tumours shrink by a predefined amount. This is assessed using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and the assessment is done by blinded independent central review (BICR), meaning the reviewers do not know which treatment each participant received.
What side effects are known?
A systematic review and meta-analysis of cadonilimab safety has been published, but the available source material for this page does not include the detailed side-effect findings from that review. The review confirms that cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, but specific common and serious side effects are not reported in the source provided.