Personalized Targeted Glioblastoma Therapies by ex Vivo Drug Screening

Inclusion Criteria:

• Age 18-75

• ECOG performance status 0-2

• Newly diagnosed glioblastoma, IDH wildtype - according to the 2021 WHOclassification of Tumors of the Central Nervous System

• MGMT promotor unmethylated per local investigator

• Tissue available for drug screening (successful PDC establishment from surgicalmaterial)

• Scheduled for concomitant radio-chemotherapy with temozolomide

• Written informed consent

Exclusion Criteria:

• Current participation in another therapeutic clinical trial

• Patients with a concurrent malignancy or malignancy within five years prior of studyenrolment except for carcinoma in situ of the cervix, non-melanoma skin carcinoma orstage I uterine cancer within the last 3 years

• Pregnant or lactating women

• Current known infection with hepatitis B virus (HBV), or hepatitis C virus (HCV).Patients with past HBV infection or resolved HBV infection (defined as having anegative hepatitis B surface antibody [HBsAg] test and a positive anti-hepatitis Bcore antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible.Patients positive for anti-HCV antibody are eligible only if polymerase chainreaction (PCR) is negative for HCV RNA.

• Known human immunodeficiency virus (HIV) infection that is not well controlled. Allof the following criteria are required to define an HIV infection that is wellcontrolled: undetectable viral RNA, CD4+ count ≥350 cells/mm3 , no history ofAIDS-defining opportunistic infection within the past 12 months, and stable for atleast 4 weeks on the same anti-HIV medications (meaning there are no expectedfurther changes in that time to the number or type of antiretroviral drugs in theregimen). If an HIV infection meets the above criteria, monitoring of viral RNA loadand CD4+ count is recommended.

• Any of the following co-morbidities:

• Pre-existing severe peripheral neuropathy (> CTCAE grade 2)

• Hepatic impairment (Bilirubin Level >1.5x-3x ULN)

• Kidney dysfunction (CrCl < 59 mL/min)

• Cardiac dysfunction with left ventricular ejection fraction <60 %

• Any grade of interstitial lung disease

• Ongoing or previous history of rhabdomyolysis

• Acute pancreatitis

• QTcF ≥480 msec

• Diabetes mellitus with fasting glucose > 250mg/dl or 13.9 mmol/L

• Participants who are unable or unwilling to comply with the requirements of theprotocol as assessed by the investigator.