Trial design
Een fase II studie die de intracraniële effectiviteit van tarlatamab evalueert bij patiënten met kleincellig longcarcinoom en asymptomatische actieve uitzaaiingen in de hersenen

The tarlatamab dose is based on the DeLLphi-30112 and -304 study (NCT05740566)14: tarlatamab 1 mg iv on day 1, followed by 10 mg iv on days 8 and 15, and Q2W in a 28-day schedule thereafter. Patients will be treated until disease progression, unacceptable toxicity, death or withdrawal of consent. If a patient experiences (oligo)progression in the brain and still has clinical benefit according to the inves-tigator, then radiotherapy to the brain with afterwards continuation of tarlatamab is allowed upon discussion with the sponsor.

Primaire doel

• De respons (afname) van de hersenmetastasen op tarlatamab evalueren met de Response As-sessment in Neuro-Oncology (RANO)-hersenmetastasen criteria
• Belangrijkste eindpunt van de studie
   Hersenmetastasen respons (afname, RANO-hersenmetastasen

Key eligibility: signed and written informed consent, age 18 years or older, pathology proven meta-static SCLC pretreated with at least platinum-doublet chemotherapy with or without immunotherapy, no maximum of previous lines of systemic therapy, ECOG PS 0-1, estimated life expectancy 12 weeks or more, at least one asymptomatic active (i.e. newly diagnosed or unequivocally progressive) un-treated brain metastasis ≥ 5mm, adequate organ and bone marrow function, BM not in eloquent area (to be discussed with neuro-oncologist), no leptomeningeal metastases on MRI brain, no contra-indi-cation for tarlatamab, no previous treatment with DLL3 targeting agent, no current grade 2 or higher toxicity from previous systemic therapy, with the exception of alopecia

Symptomatic BM (if asymptomatic with corticosteroids with a maximum dose of steroids of 10 mg prednisolone or equivalent/day, the patient is eligible). If in doubt, discussion with the sponsor is necessary

• Leptomeningeal metastases (evaluated with MRI brain)
• BM in eloquent area (to be discussed with neuro-oncologist
  -Contra-indication for MRI
• Prior history of severe or life-threatening events from any immune-mediated therapy
• Grade 2 or higher toxicity from previous systemic therapy, except for alopecia
  -Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II, appendix 2), within 6 months prior to first dose of study treatment
• History of arterial thrombosis (e.g. stroke or transient ischemic attack) within 6 months prior to first dose of study treatment
• Evidence of ILD or active, non-infectious pneumonitis
• History of solid organ transplant
• Major surgical procedures within 28 days prior to first dose of study treatment
  -Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to first dose of study treatment
  Receiving another anticancer therapy. Adjuvant hormonal therapy for resected breast cancer is permitted