Approximately 58-68 total subjects will be enrolled. In the first stage, 10 response evaluable subjects (either IDHwt or IDHm Grade 4 astrocytoma) will be enrolled. If 1 or more of the first 10 response evaluable subjects achieve an objective response, 19 further subjects may be accrued in the second stage (for a total of 29 response evaluable subjects).

Subjects enrolling in the study will provide fresh (in subjects who undergo a planned tumor resection) or archival (all subjects) tumor tissue sample (at least 10 unstained slides of 5-micron thickness) at screening for retrospective exploratory biomarker analysis and determination of intertumoral PTGR1 levels.

STAR-001 (LP-184) will be administered via IV infusion over 30 minutes on Day 1 and Day 8 of each 21-day cycle. The STAR-001 dose for this study is 0.39 mg/kg.

Spironolactone will be administered orally on Day (-2), Day (-1), and between 4-8 hours before the STAR-001 infusion on D1 (Day of STAR-001 IV infusion) and on Day 6, Day 7, and between 4-8 hours before the STAR-001 infusion on Day 8 . The spironolactone dose for this study is 100 mg given 3 times prior to STAR-001 infusion.

Patients will continue to receive treatment based on response assessment and tolerability. Patients with disease control after Cycle 1 may continue treatment with STAR-001 (LP-184) if, in the opinion of the investigator, the patient is deriving clinical benefit from continuing study treatment. Patients may continue therapy for up to two years, or withdrawal for reasons of progressive disease on imaging, clinical progression, ≥Grade 4 AEs, withdrawal of consent, loss to follow-up, protocol violation, or at the discretion of the investigator.

Treatment beyond one year, if determined by the investigator to be of clinical benefit, requires consultation with and approval by the sponsor.

After treatment has been discontinued, an end-of-treatment visit will occur 30 days (+7 days) after the final dose. Patients are to be followed for survival (via telephone contact or review of medical records every 3 months.

Inclusion Criteria:

1. Histopathology confirmed supratentorial GBM at first recurrence including both IDHwt GBM and IDHm Grade 4 astrocytoma.

2. Provision of archival tissue and in re-resected subjects, contemporaneous tissue.

3. No more than one prior systemic treatment (temozolomide + involved field radiotherapy +/- an experimental agent +/- tumor treating fields device) in IDHwt GBM

4. No more than one prior systemic therapy following diagnosis of IDHm Grade 4 astrocytoma

5. Radiographically measurable disease that can be assessed per RANO 2.0.

6. Subjects are ≥ 18 and < 70 years old at the time of informed consent with a diagnosis of progressive or recurrent GBM by MRI findings.

7. Up to 5 subjects in each Simon stage have a clinically indicated need for surgical intervention per institutional standard of care.

8. Performance status must be ≥ 70% on the Karnofsky scale within 14 days prior to enrolment.

9. Subjects on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 7 days and dexamethasone dose or equivalent steroid dose < 4 mg/day) prior to baseline screening MRI are allowed. Exception is for subjects undergoing planned tumor resection where the dexamethasone dose may be temporarily increased and subsequently tapered as clinically indicated.

10. Subject has adequate organ function, defined as follows:

    Note: Complete blood count should be obtained without transfusion or receipt of colony-stimulating factors in the 2 weeks before obtaining a sample.

    1. absolute neutrophil count ≥1,000/μL
    2. platelets ≥100,000/μL
    3. haemoglobin ≥ 8 g/dL
    4. serum creatinine clearance ≥60 mL/min
    5. total bilirubin ≤1.5× ULN or direct bilirubin ≤1 × ULN (exceptions are granted for patients with Gilbert's syndrome)
    6. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
    7. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy (PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants).
    8. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy, if the PT or PTT is within therapeutic range of intended use of anticoagulants.

11. A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

    a. Is not a woman of childbearing potential (WOCBP). OR b. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, from the Screening Visit through at least 180 days after the last dose of study drug and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. Further guidance is provided in Appendix 5. Contraceptive and Barrier Guidance. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) within 72 hours before the first dose of study drug.

    The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

12. A male subject of reproductive potential is eligible to participate if he agrees to the following starting with the first dose of study drug through at least 90 days (a spermatogenesis cycle) after the last dose of study drug:

    1. refrain from donating sperm.

       PLUS, either:

    2. be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.

    OR c. must agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak, when having sexual intercourse with a WOCBP who is not currently pregnant.

13. The Investigator, or a person designated by the Investigator, will obtain written informed consent from each study participant or the participant's legally acceptable representative, when applicable, before any study-specific activity is performed. The Investigator will retain the original copy of each participant's signed consent document.

14. Subject must provide archival tumor tissue sample at screening for retrospective exploratory biomarker analysis (see Laboratory Manual for tumor requirements). Subjects undergoing re-resection must also provide contemporaneous tumor sample at screening as well.

15. Patients have been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.

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Exclusion Criteria:

1. Any radiation therapy within 12 weeks prior to the first dose of study drug. unless the progression is clearly outside the radiation field (e.g., beyond the high-dose region or 80% isodose line) or there is pathologic confirmation of disease progression.

2. Subject has received more than 1 systemic therapy.

3. Subject has known hypersensitivity to STAR-001 (LP-184) or spironolactone, their components, or their excipients.

4. Subjects had a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include treated basal cell or localized squamous cell skin carcinoma, localized prostate cancer, or other localized carcinomas such as carcinoma in situ of cervix, breast, or bladder.

5. Subject is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection that requires systemic therapy. Specific examples include, but are not limited to, history of (non-infectious) pneumonitis that required steroids or current pneumonitis, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining consent).

6. Subject has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the subject's participation for the full duration of the study treatment including the following:

   a. Subjects who received colony-stimulating factors (e.g., granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks prior to the first dose of study drug are not eligible.

7. Subject has a known history of HIV (type 1 or 2 antibodies).

8. Subject has known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative] is detected). Subjects with treated hepatitis C are permitted.

9. Subject is currently participating and receiving an investigational agent.

10. Subject has not recovered (i.e., to Grade ≤1 or to baseline) from cytotoxic therapy-induced adverse events (AEs). Note: Subjects with Grade ≤2 neuropathy, Grade ≤2 alopecia, or Grade ≤2 fatigue is an exception to this criterion and qualify for the study.

11. Subject had treatment with prior systemic anticancer therapy within the 4 weeks prior to the first dose of study drug, or

12. Subject has received a live vaccine within 14 days of planned start of study drug.

13. Subject has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, and history of cerebrovascular accident) within 3 months prior to screening.

14. Subject has heart rate-corrected QT interval prolongation >480 ms (average of triplicate ECGs) by Fredericia at screening except for a documented bundle branch block or unless secondary to pacemaker. In the case of a documented bundle branch block or a pacemaker, discussion with the medical monitor is required prior to enrolment.

15. Patient is on medication that increases serum potassium (e.g., triamterene, propanolol or medications with labeled DDIs with spironolactone (e.g., digoxin).

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