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

NCT06807307 | Recruiting

• 1 other identifier: RS158/IRE/24
• Study Type: observational
• Target: 256
• Locations: 1 country
• Sites: 1

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Innovative molecular tool

  To generate an innovative molecular tool for prediction DNA/RNA will be extracted from 5μm FFPE tissue sections using the AllPrep DNA/RNA FFPE kit (Qiagen). The quality of the RNA will be evaluated with the Bioanalyzer, the integrity of genomic DNA through the Agilent NGS FFPE qPCR QC Kit (Agilent). The libraries for RNA-Seq will be prepared using the RNA TruSeq Exome Kit (Illumina). The quality of the libraries resulting will be checked using Bioanalyzer (high sensitivity DNA kit). The intermediate library before exon enrichment will be quantified with Qubit, the final library with qPCR. The samples will be sequenced in paired-end mode, sequencing 76 bp on each side. The Exome DNA sequencing will be performed using SureSelectXT Low Input Kit reagents for the initial preparation of the library followed by enrichment with Clinical Research Exome Kit (Agilent).

  24 months

Secondary Outcomes (2)

• Tracing the evolutionary path

  24 months

• Identification of therapeutic vulnerabilities specific

  24 months

Study Arms (2)

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.

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Regina Elena Cancer Institute: lead

Study Sites (1)

IRCCS National Cancer Institute "Regina Elena"

Rome, 00144, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tissue samples

Central Study Contacts

Marcello Maugeri Saccà, Medical Doctor

CONTACT

+39 06 5266 6914; marcello.maugerisacca@ifo.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2025
• First Posted: February 4, 2025
• Study Start: June 4, 2024
• Primary Completion (Estimated): June 4, 2026
• Study Completion (Estimated): June 4, 2026
• Last Updated: February 4, 2025

Record last verified: 2025-01

Locations

IT (1)