• Age ≥18 years

• Histopathologically confirmed IDH-wildtype glioblastoma, WHO Grade 4, and variants including gliosarcoma as per WHO 2021 criteria (38).

• Prior treatment with radiotherapy with or without chemotherapy.

• Recurrent or progressive disease with no more than 2 prior relapses.

• Confirmed measurable disease per RANO 2.0 for GBM.

• Tumor is documented as IDH1/2 wildtype by direct DNA sequencing, provided that it is performed in a CLIA/CAP-certified laboratory.

• Availability of archival formalin fixed paraffin-embedded (FFPE) tumor tissue block or 20 unstained FFPE slides (5 μm thick) from any prior surgery for mutation testing and additional sequencing.

• Karnofsky Performance Status of ≥ 60.

• Candidate for surgical resection.

• Tumor tissue extending to cortical gray matter based on MRI.

• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.

• Women of child-bearing potential (WOCBP), defined as any individual assigned female at birth physiologically capable of becoming pregnant, must use highly effective contraception during study treatment and for 1 month after study discontinuation. Highly effective contraception is defined as either:

‣ True Abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.

⁃ Sterilization: Surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.

⁃ Male Partner Sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female subjects on the study, the vasectomised male partner should be the sole partner for that participant.

⁃ A barrier method defined as condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository along with a second contraceptive method as described below:

• Placement of an intrauterine device (IUD) or intrauterine system (IUS)

∙ Appropriate hormonal contraceptives (including any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent - including oral, subcutaneous, intrauterine

• Male subjects should agree to use a highly effective method of contraception starting with the first dose of study therapy through 3 months after the last dose of therapy. Male subjects must not donate semen for 3 months after the last dose of study treatment.

• Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged)