In short
hu14.18K322A (also called daretabart) is an investigational humanised monoclonal antibody that targets disialoganglioside GD2 on neuroblastoma cells. It is being studied in a Phase 4 trial with 203 children and adolescents who have high-risk neuroblastoma that has relapsed or is refractory to treatment. The trial evaluates hu14.18K322A given together with chemotherapy.
Key points
- hu14.18K322A is an investigational antibody directed against GD2, a marker on neuroblastoma cells.
- The registered trial is Phase 4 and plans to enrol 203 participants aged 18 months to under 18 years.
- The trial studies relapsed or refractory high-risk neuroblastoma.
- hu14.18K322A is given by intravenous infusion together with chemotherapy.
- The main measures are overall response rate and metastatic complete response rate.
- The trial is currently authorised in the EU Clinical Trials Information System.
What is hu14.18K322A?
hu14.18K322A is an investigational humanised IgG1 monoclonal antibody. Its full name is Humanised IgG1 (K322A) monoclonal antibody against disialoganglioside GD2. The development code hu14.18K322A is used in the trial record, and the substance is also referred to as daretabart. It is a protein-based substance studied in oncology. The trial record does not list a marketing authorisation for this substance, so it is still considered investigational in this setting.
How does hu14.18K322A work?
hu14.18K322A is an antibody that recognises and binds to disialoganglioside GD2, a molecule found in large amounts on the surface of neuroblastoma cells. By attaching to GD2, the antibody is designed to help the immune system attack the tumour cells. The K322A modification in the antibody is intended to reduce certain immune-related side effects while keeping the ability to bind GD2.
Which conditions is hu14.18K322A studied for?
- Relapsed high-risk neuroblastoma: neuroblastoma that has come back during or after treatment in children and adolescents.
- Refractory high-risk neuroblastoma: neuroblastoma that has not responded to treatment, including metastatic disease.
How is hu14.18K322A given?
In the registered trial, hu14.18K322A (daretabart) is given as an intravenous infusion at a dose of 60 mg per square metre of body surface area. It is given in combination with chemotherapy, which in this trial includes irinotecan and temozolomide.
What do the clinical trials show?
The EU Clinical Trials Information System lists one authorised interventional trial for hu14.18K322A, with the identifier 2025-524397-42-00. It is a Phase 4 trial that plans to enrol 203 participants aged from 18 months to under 18 years.
The trial has two sub-protocols. Sub-protocol A measures the overall response rate, defined as the proportion of participants who achieve a complete or partial response according to the International Neuroblastoma Response Criteria, when hu14.18K322A is given with chemotherapy to participants with relapsed high-risk neuroblastoma. Sub-protocol B measures the metastatic complete response rate in participants with refractory high-risk neuroblastoma and metastatic disease.
An earlier published Phase 1 study evaluated hu14.18K322A in people with recurrent or refractory solid tumours, including neuroblastoma, and examined how the antibody behaves in the body.
What side effects are known?
The published Phase 1 study provides information on side effects of hu14.18K322A. Because the antibody activates immune cells, infusion-related reactions such as pain, fever and changes in blood pressure can occur. The K322A change was designed to reduce complement-related side effects compared with earlier anti-GD2 antibodies.