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

Inclusion criteria

• Age ≥18 years.
• Ability to provide written informed consent.
• Histologically confirmed diagnosis of DLL3 positive high-grade glioma (HGG).
• 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).
• Surgery can be safely delayed for a minimum of 2 weeks following the Day 15 (D15) administration of study immunotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• 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.

• For women of childbearing potential: negative pregnancy test at screening.
• Willingness to use highly effective contraception during treatment during treatment and for at least 60 days after the last dose of tarlatamab,

Exclusion criteria

• Candidate for biopsy only (class 4), according to the RANO resect group classification system for EOR.
• Ongoing steroid treatment at a dose >4 mg dexamethasone equivalents daily.
• 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.

• Known history of human immunodeficiency virus (HIV) infection (HIV-1/2 antibodies).
• Known active hepatitis B virus infection (hepatitis B surface antigen reactive).
• Known active hepatitis C virus infection (HCV RNA qualitative positive).
• Receipt of a live vaccine or live-attenuated vaccine within 30 days before the first dose of study treatment.
• 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,
• Pregnant or lactating women.