New treatments are needed for children with neuroblastoma or other solid tumors whose tumors do not respond to or return after standard treatment. Idasanutlin is an experimental drug that has already been studied in adults. It works by activating signals within the cancer cell that tell cancer cells to die. As a result, it could stop the growth and spread of cancer cells.
This was the first study with idasanutlin in children. The goal was to see if idasanutlin can be given safely to children, and how well it works. In this study, the drug was given alone or in combination with existing drugs (chemotherapy or venetoclax).
Disappointing efficacy
In this study, 38 children and young adults participated from six different countries in Europe and North America. The study ran from January 2020 to May 2024. In the first part of the study, participants with various solid tumors (including neuroblastoma and osteosarcoma) received idasanutlin alone. The highest dose of idasanutlin that could be safely given to children was established at 4.5 mg/kg. However, efficacy was disappointing. None of the participants had a response to treatment.
In the next part of the study, idasanutlin was given in combination with chemotherapy (cyclophosphamide and topotecan) or venetoclax to nine children with neuroblastoma. Only one of them had a response to treatment.
Side effects
Almost all participants experienced treatment side effects to varying degrees. The most common side effects were vomiting, nausea, diarrhea and decreased numbers of certain types of blood cells (platelets, red and white blood cells). Many participants (61%) experienced side effects that where serious enough to require hospital care. These included low numbers of neutrophils (white blood cells that help fight infection) combined with fever, and low numbers of platelets (blood cells needed for clotting).
Discontinued
Because too many participants experienced unwanted side effects and idasanutlin did not work as well as expected, the study was stopped early. Although involving only a small number of patients, these results have provided more information about the safe dose and efficacy of idasanutlin. For now, there are no plans for further research. Other drugs with similar working mechanisms as idasanutlin are still under investigation. If those can be dosed higher with fewer side effects it could turn out differently.
More information about this study can be found here:
Clinicaltrials.gov NCT04029688
EU clinical trials register 2018-004579-11
ForPatients - Roche