Irinotecan-ChemoSeed in Surgically Resectable Glioblastoma

Inclusion criteria

• 1. Radiologically relapsed, neuropathologically verified GBM (by the WHO 2021 criteria) (Part 1) or newly diagnosed, radiologically suspected GBM (Part 2) amenable to surgical resection.

• Male or female aged 18 years or older. 3. Ability to understand and the willingness to sign a written informed consent form (ICF).

• KPS ≥ 70. 5. Life expectancy ≥ 6 months. 6. Adequate organ and marrow function as follows (all required):
• Absolute neutrophil count ≥ 1.5 k/µL
• Platelets ≥ 100 k/µL
• Haemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.8 mg/dL or creatinine clearance > 50 mL/min
• Bilirubin ≤ 1.5 mg/dL
• Alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3.0 × ULN
• Prothrombin time ≤ 1.5 × ULN
• International normalised ratio (INR) ≤ 1.5 × ULN
• Partial thromboplastin time ≤ 1.5 × ULN 7. Women of childbearing potential must agree to use a highly effective method of contraception for the duration of the trial or for 5X the systemic half-life (i.e., 6 weeks) plus 6 months following irinotecan-ChemoSeed administration, whichever is the longest.. Female participants must refrain from egg donation during the same time period. 8. Male participants of reproductive potential, who intend to be sexually active with a female partner of childbearing potential, must commit to use barrier contraception (e.g., condom) for the duration of the trial or for 5X the systemic half-life (i.e., 6 weeks) plus 6 months following irinotecan-ChemoSeed administration, whichever is the longest. Male participants must not donate or bank sperm during the same time period.

Exclusion criteria

• 1. Multicentric disease defined by tumours which have multiple discrete areas of contrast enhancing or non-enhancing tumour without connecting T2/ fluid-attenuated inversion recovery (FLAIR) signal abnormality. 2. Diffuse leptomeningeal disease. 3. Not eligible for surgical resection. 4. Known hypersensitivity to IRN or PLGA. 5. Prior IRN treatment (for Part 2 participants) less than 12 months from trial enrolment 6. Pregnant or lactating women or participants who intend to get pregnant during the trial.

• Prior active malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to surgical resection and trial drug administration. 8. Part 1 participants with relapsed GBM: treatment with another investigational drug or other intervention within 4 weeks prior to the surgical resection or 5 times the half-life (whichever is longer) before trial drug administration. 9. Part 2 participants with newly diagnosed GBM: prior RT, chemotherapy, immunotherapy, or targeted agents administered specifically for the lesion being treated.