Inclusion Criteria:  Signed informed consent form (ICF) prior to the start of any trial-related procedures. Subject age ≥ 18 years with an upper limit of 70 years. In the Investigator's opinion, subject is able and willing to comply with all trial requirements for the duration of the trial. Suspected primary, newly diagnosed supratentorial GBM (Grade IV glioma per WHO guidelines) based on signs/symptoms and MRI (obtained maximally 10 days prior to surgery, using the same MRI settings as will be used for post-surgery MRI; if the MRI is older than 10 days or if it is taken at a local clinic, this has to be repeated within 10 days before the surgery), needing maximum safe resection followed by chemoradiotherapy as per institutional guidelines (Stupp protocol: radiotherapy [60 Gy total; 10 Gy per week for 6 weeks] plus concomitant TMZ [75 mg/m2 of body surface area per day; 7 days per week from first to the last day of radiotherapy], followed by six cycles of adjuvant TMZ [150 to 200 mg/m2] once daily for 5 consecutive days, followed by 23 days of no treatment prior to the next cycle; or CeTeG protocol for MGMT promoter methylated GBMs: up to six courses of lomustine [100 mg/m2 on Day 1 plus TMZ [100-200 mg/m2 per day on Days 2-6 of the 6-week course] in addition to radiotherapy [59-60 Gy], if preferred by the investigator). Preliminary histological diagnosis of GBM by an intraoperative "frozen section", analyzed during surgery is mandatory before administration of SI-053. A final diagnosis is made by histopathological and molecular analysis of the resected tumor tissue. It is the surgeon's estimation that maximum safe resection of the contrast enhancing part of the tumor with image-guided surgery is possible and it is not expected that the ventricular system will be opened during surgery. When the ventricular system is opened during surgery, no SI-053 will be administered. The tumor volume as assessed by pre-surgery MRI is at least 10 mL, and the actual resection bed volume based on the surgeon's estimation after surgery enables complete administration of a single dose of SI-053. Karnofsky Performance Status (KPS) score ≥70% Women of childbearing potential (WOCBP) and men whose partner is of childbearing potential must use effective contraception from the time of screening and for 6 months after receiving SI-053. WOCBP should have a negative serum pregnancy test β-human chorionic gonadotropin (β-HCG) at trial enrollment and within ≤ 72 h before SI-053 administration.  Subjects must have following laboratory values obtained within 2 weeks prior to enrollment.  • Acceptable liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except in the case of Gilbert's disease); Albumin 3.0 - 5.5 g/dL; Aspartate transaminase (AST) ≤ 2.5 x ULN  Alanine transaminase (ALT) ≤ 2.5 x ULN Alkaline phosphatase ≤ 2.5 x ULN Acceptable kidney function: Creatinine clearance: ≤ 30 mL/min (by CKD-EPI formula) Acceptable hematologic status:  Absolute neutrophil count (ANC) ≥ 1 500 cells/mm3 Platelet count ≥ 100 000 cells/mm3 Hemoglobin ≥ 10.0 g/dL  Subjects should have a suspected life expectancy of at least 6 months.  Exclusion Criteria:  Subjects who fulfil any of the following criteria will be excluded from the trial:  Prior treatment for GBM including resection or radiation therapy. Contraindications to radiation therapy or TMZ chemotherapy (i.e allergy, hypersensitivity or other intolerabilities to TMZ and its excipients or hypersensitivity to dacarbazine).  Has a history of another primary malignancy, except for:  Malignancy treated with curative intent and with no known active disease within 2 years prior to SI-053 administration Adequately treated non-invasive basal skin cancer or squamous cell skin carcinoma Adequately treated uterine cervical cancer stage 1B or less  Has clinically significant cardiac disease (as identified by electrocardiogram [ECG]), including:  Known congestive heart failure Grade III or IV by the New York Heart Failure Association; Myocardial infarction within 6 months prior to signing the ICF; Onset of unstable angina within 6 months prior to signing the ICF. Infratentorial or multifocal glioblastoma. Pre-operative MRI showing ventricular invasion (defined as presence of intraventricular lesion or of intraventricular tumor mass). Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1. Chronic use of systemic steroid therapy (>1 month of >10 mg prednisone per day or equivalent, except topical or inhaled). Any significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or affect the participant's ability to participate in the trial. Subjects who have participated in another research trial involving an investigational product within the past 12 weeks or are currently participating in another clinical trial (excluding observational studies). Pregnant or lactating women. Subjects unable to undergo MRI during the trial participation