PaedNeoVax (ANZCHOG2511)

Multicentre, investigator-initiated phase I/II clinical trial to assess safety and efficacy of personalised mRNA vaccine targeting tumour-associated neoantigens in children and young adults with high-risk brain tumours: the PaedNeoVax study

Trial Summary

Brief description of the study purpose:
This study is investigating a personalised mRNA vaccine for children and young people with high risk central nervous system tumours. The vaccine is made individually for each participant using information from their tumour and is designed, based on laboratory and preclinical research, to help the immune system recognise proteins associated with the tumour.

Who is it for?
You may be eligible if you are male or female 6 months to 25 years old, have a high-risk central nervous system tumour, and are enrolled in the ZERO Childhood Cancer molecular profiling program, you have measurable disease (with some exceptions for newly diagnosed cases), a Karnofsky/Lansky score of more than 50, a life expectancy of at least 12 weeks, have recovered from prior therapy according to required washout periods, and have adequate blood counts, kidney function, liver function, and coagulation. You must not have a known hypersensitivity to mRNA vaccines, not be pregnant or breastfeeding and have no underlying congenital immunodeficiency. You must not be taking corticosteroids other than physiologic replacement doses and have no live vaccines within 3 months of starting protocol therapy.

Study details:
Participation in this study involves testing a new, personalised mRNA vaccine, designed to help the individual’s immune system fight certain types of brain and spinal cord tumours. The treatment involves receiving 9 doses of the vaccine administered over 6 months. The study is divided into two parts, called phases. Participants taking part in this study will be in either Phase 1 or Phase 2. The treatment is the same in both parts of the study with only the dose being different in phase 1 vs phase 2. Each phase will take place one after the other:
• Phase 1 will be completed first and will determine the vaccine’s safety and the ideal dose. This will occur by starting at a low dose and increasing the dose in these participants until a safe and effective dose is established.
• Once Phase 1 is complete, Phase 2 will begin and will test how well the vaccine works at the dose determined in Phase 1.

PTX-108 is a personalised mRNA anti-tumour vaccine designed for the treatment of young patients with brain cancer. The vaccine comprises an individualised mRNA sequence encapsulated in a common lipid nanoparticle. This phase I/II clinical trial will investigate the safety and efficacy of the personalised PTX-108 mRNA cancer vaccine in paediatric and young adult patients with high-risk brain tumours including relapsed or refractory high-grade tumours and patients with newly diagnosed Diffuse Midline Glioma (DMG) following completion of radiation therapy.

Phase I of the trial will evaluate safety of the personalised vaccine and establish the recommended phase II dose (RP2D).
Phase II will be a stratified expansion phase. Phase II Stratum A will include patients with newly diagnosed DMG, with outcomes compared to matched historical cohorts from the international DIPG Registry (iDIPGR), who were diagnosed after 2010, and have genomic, clinical and survival data available. Phase II Stratum B will include patients with other high-risk or relapsed/refractory brain tumours, with outcomes analysed descriptively.

Site Status

Queensland Children's Hospital (QLD)

John Hunter Children's Hospital (NSW)

Sydney Children's Hospital (NSW)

Monash Health Clayton (VIC)

Royal Children's Hospital (VIC)

Women's and Children's Hospital (SA)

Perth Children's Hospital (WA)

Royal Hobart Hospital (TAS)

Children's Hospital at Westmead (NSW)

Starship Children's Hospital (NZ)

Christchurch Hospital (NZ)

Preparing to Open

Open

Temporarily Closed

Closed

Complete

Adult Sites These sites are not monitored. Status may vary.

Diagnosis Stage Newly Diagnosed, Relapsed/Refractory

Open Date N/A

Conditions Newly diagnosed Diffuse Midline Glioma (DMG)
Relapsed/refractory high grade brain tumours, including relapsed DMG
Newly diagnosed p53-mutant sonic hedgehog (SHH) Medulloblastoma, posterior fossa group A (PFA), Ependymoma with 6q deletion and/or 1q gain
Other high-risk paediatric brain tumours after discussion with the study committee

Patient Range 6 months25 years

Disease Type Brain and Spinal (Central Nervous System) Tumours

Study Type Interventional

Funders

ANZCHOG acknowledges the valuable support of PaedNeoVax (ANZCHOG2511) by:

Medical Research Future Fund (MRFF), Robert Connor Dawes Foundation