Tarlatamab Treatment Before and After Surgery in Surgically Resectable Recurrent High-grade Glioma: a Window of Opportunity Study (TARLAGLIA Study)

Inclusion Criteria:

1. Age ≥18 years.
2. Ability to provide written informed consent.
3. Histologically confirmed diagnosis of DLL3 positive high-grade glioma (HGG).
4. Candidate for neurosurgical resection of HGG, either in the category of supramaximal contrast-enhancing (CE) resection (class 1), maximal CE resection (class 2), or submaximal CE resection (class 3), according to the RANO resect group classification system for extent of resection (EOR).
5. Surgery can be safely delayed for a minimum of 2 weeks following the Day 15 (D15) administration of study immunotherapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
7. Adequate organ function, defined as follows:

   a. Hematological function: i. Absolute neutrophil count ≥ 1.5 x 109/L ii. Platelet count ≥ 100 x 109/L iii. Hemoglobin ≥ 9 g/dL (90 g/L) b. Coagulation function: i. prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) ≤ 1.5 x institutional upper limit of normal (ULN) except for patients receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to study entry.

   c. Renal function: i. Estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculation \> 30 mL/min/1.73 m2.

   d. Hepatic function: i. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN (or \< 5 x ULN for patients with liver involvement).

   ii. total bilirubin (TBL) \< 1.5 x ULN (or \< 2 x ULN for patients with liver involvement), except for patients with Gilbert's disease.

   e. Pulmonary function i. No oxygen supplementation. f. Cardiac function i. cardiac ejection fraction \>/= 50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no clinically significant electrocardiogram (ECG) finding.
8. For women of childbearing potential: negative pregnancy test at screening.
9. Willingness to use highly effective contraception during treatment during treatment and for at least 60 days after the last dose of tarlatamab,

Exclusion Criteria:

1. Candidate for biopsy only (class 4), according to the RANO resect group classification system for EOR.
2. Ongoing steroid treatment at a dose \>4 mg dexamethasone equivalents daily.
3. Active autoimmune disease that has required systemic treatment in the past 2 years (including disease-modifying agents, corticosteroids, or immunosuppressive drugs).

   Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is permitted.
4. Known history of human immunodeficiency virus (HIV) infection (HIV-1/2 antibodies).
5. Known active hepatitis B virus infection (hepatitis B surface antigen reactive).
6. Known active hepatitis C virus infection (HCV RNA qualitative positive).
7. Receipt of a live vaccine or live-attenuated vaccine within 30 days before the first dose of study treatment.
8. Prior malignancy within the past 3 years, except: except basal cell carcinoma or scaly skin, cervical carcinoma in situ adequately treated or other tumors treated curatively without recurrence for 3 or more years,
9. Pregnant or lactating women.