The goal of this observational study is to better understand how the immune system and certain tumor markers are linked to treatment response in patients with advanced non-small cell lung cancer (NSCLC) who receive immunochemotherapy.

The investigators aim to answer the following questions:

• Can the investigators successfully analyze immune markers and gene activity from small tumor samples (biopsies)?
• Are these markers connected to how well patients respond to immunochemotherapy and how their disease progresses?

What will participants do?

• Provide tumor tissue samples (biopsies) at key points: before treatment, about 6 weeks after starting immunochemotherapy, and if the cancer grows or treatment changes.
• Allow their tumor samples to be analyzed in the lab using advanced techniques to measure immune and genetic markers.
• Share clinical information (such as treatment response and disease progression) so investigators can study how it relates to these markers.

This study does not test a new drug or treatment.

Inclusion Criteria:

For all:

• Written informed consent of the patient
• Consent of participation in the national Network for Genomic Medicine in Lung Cancer (nNGM)
• Advanced lung cancer with non-curative treatment option (NSCLC)
• No targetable driver mutation detected, defined as no targetable drive mutation in ALK, EGFR, BRAF, HER2, MET, NTRK, RET, ROS1
• PD-L1 expression on tumor cells (TPS < 50%)

Cohort A:

• Previously untreated NSCLC without curative treatment options
• Sufficient pre-treatment tumor material available for the planned analyses or consenting and able to undergo additional pretreatment biopsy
• Scheduled to undergo immune(chemo)therapy
• Willing and able to undergo re-biopsy 6 weeks after start of immune(chemo)therapy

Cohort B:

• Any line of progression after firstline immune(chemo)therapy
• Sufficient tumor material obtained after progression on most recent line of treatment available or willing and able to undergo re-biopsy prior to next line treatment

Exclusion Criteria:

• Any condition representing an unjustified risk for obtaining an additional biopsy sample (if needed) in the view of the investigator
• Incapability of understanding the purpose and possible consequences of the trial
• Substance abuse, medical, psychological or social conditions that may interfere with the subject's cooperation with the requirements of the trial or evaluation of the study results

Participants will be adult patients (≥18 years) with histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC) who are initiating or receiving standard-of-care immunochemotherapy. Eligible participants must be able to provide tumor biopsy material at predefined time points (baseline, 6 weeks after treatment start, and/or at progression or therapy line change). Both male and female patients will be included.