Ricerca Progetti nazionali, regionali, internazionaliCORELAB

New prediCtive biOmaRkers of activity and Efficacy of immune checkpoint inhibitors in advanced non small cell Lung cArcinoma (NSCLC)

Level of PD-L1 expression tested by IHC test, is currently assessed and approved as a predictive factor for activity and efficacy of immune checkpoint inhibitors in a number of solid tumors including NSCLC and more recently urological cancer and triple negative breast cancer. Regulatory agencies have approved the diagnostic use of PD-L1 to candidate patients with advanced NSCLC to treatment with immune checkpoint inhibitors. However the cutoff of the level of expression has been established empirically and does not seem to be a reliable factor to select a subpopulation of patients who benefit from the treatment. Recently new biomarkers including level of Tumor Mutation Burden and ctDNA, have been proposed as predictive factors of response and efficacy of immunotherapy in NSCLC and other solid tumors. We hypothesise that to investigate the TMB, measured by hybrid capture-based NGS, the ctDNA and circulating tumor cells (CTC) levels and mutations, and the genetic expression profile of molecular determinants of vessel normalization (VN) in tumor patients would prove clinically useful in predicting response to immunotherapy in advanced NSCLC candidate to immunotherapy The study aims 1) To identify a reliable tissue (PD-L1) vs.  circulating and tissue new markers (ctDNA , TMB and VN) as predictive factor of activity and efficacy of  checkpoint inhibitors in patients with advanced NSCLC   and 2) To study the Angiogenesis as levels of vessel normalization (VN) factors in immune checkpoint inhibitors  (ICI) responsiveness. Patients with advanced NSCLC candidate to treatment with ICI as first or second line of treatment will be accrued in the study.

The project is a prospective evaluation of predictive factors for response and efficacy of immune checkpoint inhibitors in patients with advanced stage NSCLC. In order to perform a statistical analysis, we aim to study 150 patients. Inclusion criteria:

- Patients with diagnosis of non-operable advanced stage Lung Carcinoma

- No history of previous or concomitant other neoplastic disease

- Availability of tumor tissue for biological cell and molecular characterization

- Candidate to therapy with immune checkpoint inhibitors

- Informed consent to participate in the study

The patients will be characterized for PD-L1 on tumor tissue, Tumor Mutation Burden  classified as high, intermediate, low; Quantitative analysis of ctDNA and Circulating tumor cells at baseline, after 2, 4, 6 months and at the time of progression will be performed. Moreover the SNP of  gene encoding for PD-L1 expression and the genetic expression profile of molecular determinants of vessel normalization (VN) in tumor patients will also be analysed. End Point of the study will be the Clinical Response, Progression-free survival and Overall survival.

 

Responsabile: Pamela Pinzani

Data inizio: 07.07.20

Data conclusione: 06.01.25

CUP n. C44I18003190002

Progetto finanziato dalla Regione Toscana nell'ambito del Bando regionale Ricerca Salute 2018

 

COSTO COMPLESSIVO	CONTRIBUTO REGIONE	BENEFICIARI	PARTNER	COSTO COMPLESSIVO PER PARTNER	CONTRIBUTO REGIONE PER PARTNER
856.548,56	685.238,85	AUSL TOSCANA SUD EST	capofila	85.668,00	68.534,40
		Università degli Studi di Firenze	partner	353.500,00	282.800,00
		AOU SENESE	partner	165.856,28	132.685,02
		Università degli studi di Siena	partner	165.856,28	132.685,02
		AOU CAREGGI	partner	85.668,00	68.534,40