Whole Body HER2 Quantification With 89Zr-Trastuzumab PET/CT to Asses Zr-trastuzumab Accumulation in HER2-mutated and HER2-overexpressing Metastatic Non-small Cell Lung Cancer

The investigators investigate whether PET imaging with ⁸⁹Zr-trastuzumab can reliably demonstrate the extent of tracer accumulation in tumors of patients with HER2-mutated or HER2-overexpressing non-small cell lung cancer (NSCLC). The aim is to determine whether differences in tracer uptake can be detected between these groups, as translational studies indicate that HER2-mutated tumors may internalize trastuzumab-based agents more efficiently than tumors that solely overexpressed HER2.

Inclusion Criteria: * Signed written informed consent * Age≥ 18 years, willing and able to comply with the protocol as judged by the investigator * Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 at screening. * Patients with histologically or cytologically confirmed diagnosis of advanced stage: * HER2 overexpression, defined as an immunohistochemistry score (IHC) of 2+ or 3+ in at least 10% of tumour cells without an activating HER2 mutation * HER2 activating (insertion) mutation diagnosed through RNA sequencing (RNAseq) * Disease progression after at least one line of platinum-based chemotherapy ± immunotherapy and starting (new) systemic treatment. * Be willing to provide a recent tumor tissue specimen after the last line of therapy. Samples must be of sufficient quantity and of adequate tumor tissue content. * Able to undergo PET imaging procedures. * Measurable disease according to RECIST 1.1. * At least two measurable lesions with a long axis diameter ≥2 cm. * Adequate organ and bone marrow function within 21 days prior to tracer injection, defines as: Laboratory Test Laboratory Value Platelet count ≥100 000/mm3 or ≥100 × 109/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility) Hemoglobin ≥9.0 g/dL or 5.6 mmol/L (transfusion and/or growth factor support is allowed) Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 × 109/L Aspartate aminotransferase /alanine aminotransferase ≤3 × ULN (if liver metastases are present, ≤5 ×ULN) Total bilirubin ≤1.5 × ULN if no liver metastases (\