ID #112 PAEDNEOVAX - Multicentre, investigator-initiated phase I/II study to assess safety and efficacy of personalised mRNA vaccine targetting tumour-associated neoantigens in children and young adults with high-risk brain tumours.
Jordan Hansford, Santosh Valvi, Andrew Dodgshun, Neevika Manoharan, Cecilia Moore, Tim Hassall, Cinzia De Luca, Liz Dawes, Rebecca Goldstein, Nic Waddell, Rajiv Khanna, Ajay Taranath, Jane McEniery, Robyn Strong, Maria Kirby, Emely Hernandez, Lucy Romanoff, Trent Hummel, David Ziegler, Loretta Lau, Rajesh Krishnan, Gopalakrishna Panicker, Lilliam Oliviera, Jun Liu, Andrew Hudson, Kirstin Olsen, Charlotte Dube, Natalia Martin Orozco, Brandon WainwrightAbstract
The PAEDNEOVAX trial is a phase I/II clinical trial evaluating a personalised mRNA vaccine in children and adolescents with relapsed/refractory brain tumours (including medulloblastoma, ependymoma and high grade glioma) and newly diagnosed Diffuse Midline Glioma (DMG). This multi-centre Australian trial, in partnership with Providence Therapeutics, will determine the safety, tolerability, and preliminary efficacy of the vaccine, which is designed to target individual tumour neoantigens and tumor associated antigens. The trial leverages the ZERO2 Childhood Cancer platform for tumour Whole Genome Sequencing (WGS) and advanced bioinformatics to predict neoantigen expression, requiring ≥5 potential neoantigens. It is predicted that around 50% of these tumours will have a modest to high neoantigen load, making them potentially eligible for the trial. Personalised mRNA vaccines have demonstrated strong, emerging efficacy in poor outcome, rare cancers in adults, including pancreatic cancer and melanoma, and this trial builds on that knowledge to improve outcomes for children with brain cancer.
• Phase I will establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) (n = 4-10).
• Phase II will assess Progression-Free Survival and Overall Survival of the mRNA vaccine in two cohorts:
Stratum A – Newly diagnosed DMG (n = 45) compared to historically matched cohort by age, biology and location from the iDIPGR
Stratum B – All other diagnoses (n = 20)
• Exploratory objectives include characterising vaccine pharmacokinetics and evaluating health-related quality of life.