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

Regina Elena Cancer Institute

Status: Enrolling

Conditions: NSCLC

Study type: Observational

Funder types: Other

Identifiers

NCT06807307

RS158/IRE/24

Details and patient eligibility

About

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.

Full 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.

Enrollment: 256 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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;

Trial design

256 participants in 2 patient groups

Retrospective court of identification

Description:

The retrospective identification cohort consists of patients with metastatic disease treated with front line immunotherapy as per clinical practice from 2017 to 2021 at the IRCCS National Cancer Institute "Regina Elena". The optimal parameters for identifying KEAPness and obtaining information on the interactions between pairs of genes fundamental for the activation of KEAPness itself.

Prospective validation cohort

Description:

The validation court will collect NSCLC patients (metastatic setting, treated with first-line immunotherapy possibly in association with chemotherapy as per clinical practice) and also pancancer patients (patients with metastatic cancer other than NSCLC and who have received an ICI, either alone or in association with other medical treatments as per clinical practice), from which patients with NSCLC are excluded (PCC cohort). These patients will be recruited from the collaborating institute IRCCS Pascale of Naples. To ensure reproducibility of the study, the same approach of the first court will be applied to this one, i.e. the optimal parameters will be set for the identification of KEAPness and to obtain information on the interactions between pairs of genes fundamental for the activation of KEAPness.