PaedNeoVax - A phase I clinical trial to assess safety and efficacy of personalised mRNA vaccine for children and young adults with high-risk brain tumours

Inclusion Criteria32

• Each participant must meet all the following criteria to be enrolled in this trial:
• Age: Participant must be between 6 months and 25 years at the time of enrolment.
• Histological confirmation of one of the following high risk central nervous system tumours (either at initial diagnosis or relapsed/refractory disease):
• Any relapsed/refractory WHO grade 3 or 4 central nervous system tumour
• Newly diagnosed diffuse midline glioma in a patient anticipated to be able to start study therapy within 20 weeks post biopsy
• Newly diagnosed high risk medulloblastoma, ependymoma, or other high-risk brain tumour after discussion with the study chairs (includes p53-mutant SHH medulloblastoma, PFA ependymoma with 6q deletion and/or 1q gain or other high risk molecular alterations associated with less than 20% anticipated 5 year survival) who are anticipated to be able to proceed to PTX-108 therapy after completion of institutional standard-of-care treatment.
• Co-enrolment on the Zero Childhood Cancer (ZERO) molecular profiling platform (repeat tumour sampling in relapsed patients to obtain a current representative sample), with successful tumour WGS +/- RNA-seq analysis with a requirement of at least five potential neoantigens or tumour-associated antigens (TAAs) for vaccine production.
• Informed consent as demonstrated by a signed and dated informed consent form completed by the participant or a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant’s behalf.
• For a participant to commence personalised PTX-108 vaccine therapy (Reassessment), participants must be re-screened within 7 days of anticipated treatment start date (28 days for imaging) and the following criteria must be met:
• Confirmation of individualised PTX-108 vaccine available at the treating site for the participant.
• Measurable disease as per RAPNO/RANO 2.0 criteria (any previously irradiated lesion needs to have progressed since prior radiation therapy except for participants with newly diagnosed DMG and other high-risk brain tumours proceeding to vaccine therapy after completion of standard frontline therapy). Newly diagnosed patients eligible for study otherwise without measurable disease can be enrolled on review with the study team.
• Lansky/Karnofsky performance score of greater than 50. Use Karnofsky for patients over 16 years of age and Lansky for patients less than 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Life expectancy of at least 12 weeks at the time of re-screening. No clinical or radiological evidence of brain herniation or significant mass effect resulting in risk of imminent neurological deterioration.
• Prior therapy: Patients must have fully recovered from prior anti-cancer therapy including
• ~Myelosuppressive chemotherapy: Greater than 21 days between prior myelosuppressive therapy and PTX-108 commencement (or more than 42 days since last dose of nitrosourea).
• ~Non-myelosuppressive anticancer agents: greater than 7 days after the last dose.
• ~Immunotherapy: greater than 42 days after the last dose
• ~Monoclonal antibodies: greater than 21 days after the last dose.
• ~Radiation therapy: greater than 4 weeks after completion of radiation including CSI but within 12 weeks of biopsy for those patients with newly diagnosed DMG.
• Haematopoietic growth factor: greater than 14 days for long acting (peg-filgrastim) or greater than 7 days for short acting growth factor.
• Adequate haematologic function defined as:
• ~Haemoglobin greater than or equal to 80 g/L (post transfusion permitted)
• ~Absolute Neutrophil Count (ANC) greater than or equal to 1.0 x109/L
• ~Absolute Lymphocyte Count greater than or equal to 1.0 x109/L
• ~Platelet count greater than or equal to 75 x109/L (cannot be post-transfusion)
• Adequate renal function defined as:
• ~Serum creatinine = Less than 1.5x institutional upper limit of normal (ULN) for age and sex
• Adequate liver function defined as:
• ~Total bilirubin = Less than 1.5 x upper limit of normal (ULN) for age
• ~AST and ALT = Less than 5 x upper limit of normal (ULN) for age
• ~Adequate coagulation (INR, PT and aPTT = Less than 1.5 times ULN)
• Investigator confirmation that the participant has no other serious medical conditions which are considered by the investigator to unacceptably increase the risk to the participant