• Cohort A, B and C :

‣ Written Informed consent

⁃ Agreement to be followed up (including on-study assessments and sample collection) every 3 months in the first 2 years and then 6 monthly.

⁃ Agreement to be followed up at a TRACERx EVO site

∙ Cohort A:

• Participants ≥18 years of age, with early stage I-IIIB NSCLC disease who are eligible for primary surgery

• Histopathologically confirmed NSCLC, or a strong suspicion of cancer on lung imaging necessitating surgery (e.g., diagnosis determined from frozen section in theatre)

• Primary surgery in keeping with NICE guidelines in (lobectomy, either open or thoracoscopic), lung parenchymal-sparing operations (segmentectomy or wedge resection) if a complete resection can be achieved, extensive surgery (bronchoangioplastic surgery, bilobectomy, pneumonectomy) if necessary to obtain clear margins, hilar and mediastinal lymph node sampling or en bloc resection)

• For participants proceeding with upfront primary surgery (i.e. no neoadjuvant therapy), a minimum tumour diameter at least 15mm to allow for sampling of at least two tumour regions

• Participants undergoing neoadjuvant treatment must have at least 1 region of fresh frozen or FFPE surgical or diagnostic biopsy tissue.

• Considered sufficiently fit for upfront standard of care primary surgery or neoadjuvant therapy if indicated

• Performance status 0 to 2

∙ Cohort B:

• Participants ≥18 years of age, with late-stage unresectable stage IIIB and above NSCLC disease (TNM 8th edition) or presenting with stage IV de novo metastatic disease.

• Sufficient tissue (at least 1 region/biopsy), either FFPE or fresh frozen

• Deemed to be fit for anti-cancer treatment

• Performance status 0 to 2 Participants who were initially consented into Cohort A with a post-surgical staging of stage IIIB/C or IV could be included in Cohort B.

∙ Cohort C:

• Participants ≥18 years of age, with any stage SCLC or pleural mesothelioma.

• Sufficient tissue (at least 1 region/biopsy), either FFPE or fresh frozen

• Deemed to be fit for anti-cancer treatment

• Performance status 0 to 2