Inclusion Criteria:
* Histologically diagnosed high-grade glioma (Grade 3 or 4 per 2021 WHO criteria) in the frontal lobe.
* Tissue must demonstrate mTOR+: PTEN loss OR PIK3C2B or AKT3 amplification on aCGH OR mutations for PIK3CA or PIK3R1, or mTOR or PTEN mutations using next-generation sequencing analysis OR pS6 positivity on immunohistochemistry (≥30% for pS6).
* Patients who have completed the Stupp regimen.
* Have measurable disease pre-operatively, defined as at least 1 contrast enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria.
* Sufficient biopsy or archival tissue to confirm eligibility
* Has voluntarily agreed to participate by giving written informed consent. Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
* Age ≥18 at time of consent.
* Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale
* Participant has adequate bone marrow and organ function
* Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
* For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation until the end of treatment administration and for 3 months after the last dose of study drug.
* For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner until the end of treatment administration and for 3 months after the last dose of study drug.
* Agreement to adhere to Lifestyle Considerations throughout study duration
Exclusion Criteria:
* Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
* Pregnancy or lactation.
* Known hypersensitivity to temsirolimus or its metabolites, polysorbate 80, or to any other component of temsirolimus.
* Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, active infection, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance\]
* Received a live vaccination or is in close contact with someone who received a live vaccination within 28 days of the start of study treatment
* Treatment with another investigational drug or other intervention within 30 days prior to the planned treatment Day 1.
