Clinical trial NCT06807307: Transcriptional Framework for the Molecular Diagnosis of Response to Immunotherapy in Lung Cancer With Agnostic Potential
Official title: KEAPnes: Transcriptional Framework for the Molecular Diagnosis of Response to Immunotherapy in Lung Cancer With Agnostic Potential
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: NSCLC
Lead sponsor: Regina Elena Cancer Institute
Sponsor class: OTHER
First posted: 2025-02-04
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with metastatic NSCLC who are candidates for and/or undergoing treatment first-line chemotherapy-immunotherapy combination treatment or immunotherapy from alone (if PD-L1\>50% as per clinical practice) that meet the following criteria.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Innovative molecular tool
timeFrame: 24 months
Secondary outcomes:
measure: Tracing the evolutionary path
timeFrame: 24 months
measure: Identification of therapeutic vulnerabilities specific
timeFrame: 24 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: IRCCS National Cancer Institute "Regina Elena"
Study officials:
References: