The study aims include:

• Exploring potential predictive molecular profiles to immunotherapy/chemotherapy
• Investigating the role of circulating tumor DNA as a dynamic biomarker during immunotherapy/chemotherapy
• Identifying possible resistance mechanisms to immunotherapy/chemotherapy

Materials and methods:

Approximately 150 patients diagnosed with metastatic NSCLC assigned for immunotherapy or chemotherapy will be candidates for inclusion during a 1-2 years period.

A comprehensive molecular profiling will be made from the diagnostic biopsy. Before every treatment-cycle a blood sample will be taken to quantify ctDNA. At time of progressive disease during/after first line treatment, patients will be asked to participate in a new biopsy and a comprehensive molecular profiling will be performed.

The tissue and blood samples collected will be stored in a biobank. Clinical data will be collected to perform a comprehensive database.

Analysis:

Potentially predictive molecular profiles for immunotherapy/chemotherapy will be found by comparison of treatment outcome for patients with specific molecular characteristics.

Through quantification of ctDNA during treatment and upon progression, the role of ctDNA as a dynamic biomarker will be further strengthened.

Differences in molecular profiles pre- and post-treatment may reveal resistance mechanisms to treatment. Molecular profiling on progression can be valuable in second-line treatment guidance.

Inclusion Criteria:

• Age > 18 years
• Able to understand and read Danish
• WHO Performance status 0-2
• Acceptable organ function (liver/kidney/heart) for treatment
• The disease has to be:

evaluable or measurable according to RECIST/iRECIST accessible for biopsy metastatic or not suitable for curative intended treatment

Exclusion Criteria:

• Other active cancers
• Contraindications for systemic therapy
• ALK-positive, ROS-1 or EGFR mutations

Metastatic non-small cell lung cancer.