| Project title | A Pilot Study of Nivolumab in Paediatric Patients With Hypermutant Cancers |
|---|---|
Grant Amount | $86,796 |
Institution | Monash University |
Investigator Team | Principal investigators A/Prof. David Ziegler, Dr. Eric Bouffet and Dr. Daniel Morgenstern, with associate investigators Prof. Stewart Kellie, Dr. Maria Kirby, Dr. Timothy Hassall and Ms. Robyn Strong |
Grant Type | 2018 Clinical Trial Grant |
Years | 2018 – 2021 |
Immunotherapy is revolutionising cancer treatment, using the body’s own immune system to fight cancer. A number of new agents are available, including nivolumab, an immune checkpoint inhibitor, which has shown extraordinary results in a range of highly aggressive adult cancers. Cancers that respond well to nivolumab treatment are usually “hypermutant” – they have an extremely high number of tumour mutations.
The Zero Childhood Cancer precision medicine program, also supported by Cure Brain Cancer Foundation, has shown that up to 5% of paediatric cancers are hyper mutant, occurring more frequently in relapsed and recurrent cancer. The vast majority of these hypermutant tumours are brain cancers. Preliminary data from A/Prof. Ziegler’s collaborators in Toronto has shown that these paediatric hypermutant tumours respond dramatically to treatment with checkpoint inhibitors.
Excitingly, these international colleagues have invited A/Prof. Ziegler and his team to join their first pilot trial to test the efficacy of nivolumab for children with hypermutant tumours. It is hypothesised that children with recurrent and refractory hypermutant tumours will respond to nivolumab treatment, leading to improved outcomes. The research team will use complex bioinformatics tools, detailed analysis of immune cells and continuous monitoring of blood tests to develop robust tools to predict which patients benefit most and to monitor tumour response to immunotherapy. The trial will utilise the Australian sequencing platform of Zero Childhood Cancer using precision medicine to determine the tumour mutational burden of patients enrolled on the PRISM trial. Bristol-Myers Squibb will provide the investigational agent. This trial will provide the first data to examine the use of checkpoint inhibitors in children with recurrent and refractory hypermutated cancers, and providing a new treatment option desperately needed for these patients.
“We have treated several patients with ‘hypermutated’ tumours and seen dramatic effects. We are now partnering with our colleagues in Canada to expand access to this breakthrough treatment to children from around Australia based on an in-depth genetic profiling of their tumour.”