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

NCT ID: NCT06807307

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 256 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-04
• Study Completion Date: 2026-06-04

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.

Conditions

NSCLC

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Retrospective court of identification

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.

No interventions assigned to this group

Prospective validation cohort

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

• 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

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regina Elena Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

IRCCS National Cancer Institute "Regina Elena"

Rome, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Marcello Maugeri Saccà, Medical Doctor

Role: CONTACT

marcello.maugerisacca@ifo.it

+39 06 5266 6914 ext. +39

Facility Contacts

Marcello Maugeri Saccà, Medical Doctor

Role: primary

marcello.maugerisacca@ifo.it

+39 06 5266 6914 ext. +39

Other Identifiers

RS158/IRE/24

Identifier Type: -

Identifier Source: org_study_id