Immune Metabolism Dysregulation and Efficacy to Anti-PD-1 PD-L1 Agents in Non Small Cell Lung Cancer Patients

Prospective, biological, observational study involving the collection and use of samples from patients suffering from NSCLC lung cancer, aimed at comparing the molecular profile related to metabolism among subjects with response or resistance to checkpoint inhibitors immune system (ICI), in order to contribute to define response biomarkers and new molecular pathways as therapeutic targets combine with ICI to overcome resistance.

Study Overview

• Status: Recruiting
• Conditions: Nsclc

Detailed Description

This study aims to identify the metabolic pathways related to the tumor microenvironment in NSCLC patients and their role in the response to ICI.

To this end, the metabolic picture will be evaluated on tumor-associated fibroblasts and macrophages tumor-associated and tumor-infiltrating lymphocytes, obtained from tissue samples of two different cohorts of patients candidate to receive immune-checkpoint treatment inhibitors. Furthermore it will correlate metabolic alterations in tumor tissues and peripheral immune cells or in plasma proteins of NSCLC patients with clinical response to ICIs.

For this purpose, serum/plasma and peripheral blood mononuclear cells (PBMC) will be isolated from the peripheral blood of patients to carry out phenotypic, metabolic and transcriptional studies on cells peripheral immune system. Finally it will come explored the therapeutic modulation of metabolic signatures identified in ex vivo models, using organoids and cultures of organotypic tissue sections obtained from patients affected by NSCLC, subjected to curative surgical treatment and treatment naive.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Lorenza Landi, Doctor; Phone Number: +39 06 5266 5699; Email: lorenza.landi@ifo.it

Study Locations

• Italy
  • Rome
    • Rome, Rome, Italy, 00144
      • Recruiting
      • IRCCS National Cancer institute
      • Contact: Lorenza Landi, Doctor; Phone Number: +39 06 5266 5699; Email: lorenza.landi@ifo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from NSCLC lung cancer

Description

Inclusion Criteria:

• Age > 18 years
• Histological diagnosis of advanced stage NSCLC
• Histotype adenocarcinoma and squamous carcinoma
• ECOG PS <2
• Known PDL-1 stage
• Measurable disease
• Availability of tumor tissue
• No evidence of molecular drivers
• Written informed consent (to the study and data processing)

For the second cohort in addition to the precedents it is included

• Diagnosis of limited or locally advanced NSCLC deemed resectable

For the third cohort in addition to the precedents it is included

• patients candidates for surgery for non-small cell lung cancer

Exclusion Criteria:

• Contraindications to immunotherapy
• Unavailability of tumor tissue
• Histotype with neuroendocrine or mixed component

For the second cohort

• Contraindication to immunotherapy
• Histotype with neuroendocrine or mixed component
• Locally advanced disease candidate for concomitant chemo-radiotherapy treatment

For the third cohort

• previously treated patients

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Serum collection; Collection of sera/plasma from 400 patients, present in the Institute's Biobank. These are cells peripheral blood mononuclear cells (PBMC) and 150 tumor-infiltrating lymphocytes, cells immune cells that infiltrate adjacent non-tumor tissue and autologous CAFs from patients admitted to the IRE Institute for curative surgery. 20% of these patients relapse and access treatment Oncology Unit to be treated with immunotherapy according to the guidelines. This allows the availability on archive of tumor tissue, PBMC, CAF and TIL frozen at the time collected of the intervention who, at the time of progression, will begin treatment with ICIs according to clinical guidelines
Neoadjuvant treatment; Tissue taken will be collected, as per clinical practice, to curative surgery and when available to diagnostic biopsy. We plan to biobank in prospective manner: PBMC and plasma at the start of neoadjuvant treatment, the day before of surgery and during clinical follow-up with a pattern of every 3 months for at least 6 months of follow up and where possible up to 21 months. Evaluation of the response will be carried out by analysis of the pathological response in surgical tissue according to conventional criteria.
Tissue samples; Collection of fresh tissue samples from treatment-naïve patients undergoing surgery for NSCLC. Which will be prospectively biobanked, particularly PBMC and day-ahead plasma of the surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival OS	The application of spatial transcriptomic approaches will enable the discovery of specific cellular niches that may be responsible for mechanisms of sensitivity or resistance to ICI. With the results you get, you will probably have a chance to locate it new and wonderful metabolic pathways capable of exerting their anti-tumor effect even in combination with ICIs.	24 months

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Collaborators: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
• Investigators: Principal Investigator: Lorenza Landi, Doctor, IRCCS National Cancer institute

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2024
• Primary Completion (Estimated): July 24, 2026
• Study Completion (Estimated): July 24, 2026

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: RS196/IRE/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No