A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (GBM AGILE)

• Drug: Temozolomide
• Drug: Lomustine
• Drug: Regorafenib
• Radiation: Radiation
• Drug: Paxalisib
• Drug: VAL-083
• Drug: VT1021
• Drug: Troriluzole
• Biological: ADI-PEG 20

Newly Diagnosed Inclusion Criteria:

• Age ≥ 18 years.
• Histologically confirmed Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resectionsurgical removal of tissue or part/all of an organ or biopsyremoval of a section of tissue to analyse for cancer cells. An MRI scan with the required imagingtests that create detailed images of areas inside the body sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence or the MRI scan performed for radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells planning may serve as the MRI scan performed during screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening if all required imaging sequences were obtained.
• Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
• Availability of tumor tissuea group of cells that work together to perform a function representative of GBM from definitive surgery or biopsy.

Recurrent Inclusion Criteria:

• Age ≥ 18 years.
• Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) at first or second recurrenceto occur or happen again after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
• Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
• Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
• Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
• Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.