Transcriptional Framework for the Molecular Diagnosis of Response to Immunotherapy in Lung Cancer With Agnostic Potential

Retrospective-prospective, non-pharmacological, biological, multicenter observational study, for which the collection and use of tissue samples from patients suffering from NSCLC and/or other tumor types. Through genomic and transcriptomic sequencing techniques (whole exome sequencing, WES; whole transcriptome sequencing, WTS) patients with enrichment for KEAPness and specific gene interactions associated with it. Subsequently, through the same techniques, applied to different tumor regions taken from operating site it will be possible to identify the evolution of the tumor at a spatio-temporal level and the immune subtype associated with the presence/absence of KEAPness. Finally, cell lines will be used to recapitulate what was observed in the patient and per-patient cohorts identify new pharmacological vulnerabilities associated with the characteristics of KEAPness.

Inclusion criteria

cohort (NSCLC-IC):

• Age >18 years;
• Histological diagnosis of NSCLC
• metastatic disease
• Availability, at the time of enrollment, of adequate biological material to be able to perform molecular analyses, taken (surgical or by biopsy) before administration of any anti-tumor treatment (chemotherapy and/or radiotherapy);
• ECOG PS 0-2;
• Adequate hematological, hepatic and renal function;
• Measurable disease according to RECIST criteria
• Availability of follow-up data for at least 6 months and/or until death/progression

Exclusion criteria

cohort (NSCLC-IC):

• Previous systemic therapy for metastatic disease;
• Comorbidities not controlled with adequate medical therapy.

Inclusion criteria

NSCLC-VC cohort:

• Age >18 years;
• Histological diagnosis of NSCLC
• metastatic disease
• Availability, at the time of enrollment, of adequate biological material to be able to perform molecular analyses, taken (during surgery and/or by biopsy) before administration of any anti-tumor treatment (chemotherapy and/or radiotherapy);
• ECOG PS 0-2;
• Adequate hematological, hepatic and renal function;
• Measurable disease according to RECIST criteria;
• Written informed consent (participation in the study and data processing)

Exclusion criteria

NSCLC-VC cohort:

• Previous systemic treatment for metastatic disease;
• Comorbidities not controlled with adequate medical therapy;