BGB-58067 in Newly Diagnosed Glioblastoma Patients With MTAP-Deleted Tumors

Inclusion Criteria:

* 1\. Suspected newly diagnosed glioblastoma according to 2021 WHO criteria who have not received any tumor directed intervention other than biopsy.
* 2\. Has measurable disease (preoperatively), defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.
* 3\. Age ≥ 18 at time of consent.
* 4\. Has a performance status of ≤ 2 on the ECOG scale.
* 5\. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):

  1. Adequate Bone Marrow Function Absolute neutrophil count ≥ 1500/μL (≥ 1.5 x 109/L) Platelets (at time of surgery) ≥ 100,000/μL (≥ 100 x 109/L) Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without pRBC transfusion within prior 2 weeks.)
  2. Adequate Hepatic Function Total Bilirubin ≤ 1.5x ULN (Participants with Gilbert's syndrome with a total bilirubin ≤ 3x ULN and direct bilirubin ≤ 1.5x ULN will be permitted.) AST (SGOT) ≤ 2.5x institutional ULN (Participants with liver metastases with ALT \< 5x ULN will be permitted) ALT (SGPT) ≤ 2.5x institutional ULN (Participants with liver metastases with ALT \< 5x ULN will be permitted.)
  3. Adequate Renal Function eGFR ≥ 60 mL/min/1.73 m2 (Calculated as individualized eGFR using the CKD-EPI formula \[2021\]) If measured or calculated GFR (e.g., creatinine clearance; mGFR) is required or used: ≥ 60 mL/min
  4. Adequate Metabolic Function Albumin ≥ 2.8 g/dL
  5. Adequate Coagulation INR or PT and aPTT ≤ 1.5x ULN
* 6\. For females of childbearing potential:

  1. Must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment (within 24 hours of first dose of study treatment); in rare cases where hCG is suspected to be elevated in the absence of pregnancy (e.g., due to a tumor producing hCG), an ultrasound must be performed to rule out possible pregnancy.
  2. Must use a highly effective method of contraception (with a failure rate of \<1% per year and low user dependency) for at least 28 days prior to treatment, and agree to use such a method during study participation and for an additional 6 months after final study drug administration.
  3. Agrees not to breastfeed starting at screening, during study participation, and for 6 months after final study drug administration.
  4. Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction starting at screening, during study participation, and for 6 months after final study drug administration.
* 7\. For females of non-childbearing potential, is no longer of childbearing potential due to surgical, chemical, or natural menopause.
* 8\. For males:

  1. Agrees not to donate sperm starting at screening, during study participation, and for 3 months after final study drug administration.
  2. Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agrees to remain abstinent starting at screening, during study participation, and for 3 months after final study drug administration.

OR Must use a male condom and their female partner must use an additional highly effective method of contraception (with a failure rate of \<1% per year and low user dependency) starting at screening, during study participation, and for 3 months after final study drug administration.

* 9\. Agrees to adhere to protocol defined Lifestyle Considerations throughout study duration.
* 10\. Able and willing to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
* 11\. Understands the informed consent document and has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). 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.

Exclusion Criteria:

* 1\. Unable to undergo MRI of the brain with intravenous (IV) contrast.
* 2\. Has a known active systemic bacterial infection (on IV antibiotics or has fever \> 38.5°C at time of initiating study treatment) or fungal infection, or has a detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[e.g., hepatitis B surface antigen positive\]). NOTE: Screening of viral infection is not required for enrollment.
* 3\. Has cardiovascular abnormalities including:

  1. LVEF \< 50%
  2. History of prolonged QTc, or QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation \> 480 msec, except for right bundle branch block.
  3. Uncontrolled/symptomatic or significant cardiovascular conditions within 6 months prior to enrollment, including but not limited to any of the following: cardiac angioplasty or stenting, unstable angina pectoris, myocardial infarction, stroke/transient ischemic attack, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, New York Heart Association (NYHA) class III or IV congestive heart failure, pericarditis, atrial fibrillation or other arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).
* 4\. Has symptomatic or radiographic leptomeningeal disease.
* 5\. Has other known concurrent severe psychiatric and/or uncontrolled medical condition that, in the investigator's judgment, would cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol.
* 6\. Has received prior treatment with another investigational drug or other intervention within 5 half lives of the investigational product, whichever is longer.
* 7\. Has received prior treatment with another PRMT5 inhibitor.
* 8\. Has known allergic reactions to components of BGB-58067.
* 9\. Patients who require ongoing treatment with a strong CYP3A or CYP2C8 inhibitor or inducer, ≤ 5 half-lives or ≤ 14 days, whichever is shorter or known. Consider using alternative medications, per Investigator judgment.
* 10\. Has received a live/attenuated vaccine within 30 days of anticipated first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted.
* 11\. Is pregnant or breastfeeding.