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

This is an open-label, multi-center, Phase 0/2 trial designed to enroll up to 78 total participants with suspected newly diagnosed glioblastoma (nGBM) who are scheduled for surgical resection to accrue at least 14 participants in Arm A and 10 participants in Arm B. The trial will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of BGB-58067. The study is composed of a Phase 0 and expansion Phase 2 component. The Phase 0 primary endpoint will be suppression of symmetric dimethylarginine (SDMA) in tumor tissue measured by immunohistochemistry (IHC). The Phase 2 primary endpoint will be 12-month overall survival rate (OS12). The Phase 0 secondary endpoint will be to characterize the PK of BGB-58067 in tumor tissue, plasma, and cerebrospinal fluid (CSF). The Phase 2 secondary endpoints will include assessing the safety profile of BGB-58067 and evaluating clinical efficacy of BGB 58067 using overall survival (OS) and the 6-month progression-free survival rate (PFS6) estimated by Kaplan-Meier (K-M) methods.

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 \