Analysis of Biological Characteristics of Advanced ALK-rearranged NSCLC

BioEXALK is a prospective study evaluating the biological characteristics of advanced ALK-rearranged NSCLC treated with new generation TKIs in first line, included in the national EXPLORE ALK cohort (GFPC 03-2019).

Explore ALK GFPC 03-2019 is a non-interventional, national, multi-center cohort of ALK-rearranged NSCLC patients, whose RCB reference is 2020-A00771-38 and which obtained an approval from the IDF II Ethic Committee on 25/05/2020. Biological analysis will be performed on tissue at diagnosis and at the time of disease progression when available and on circulating tumor DNA (ctDNA) on three timepoints (diagnosis, at first tumor evaluation and at the time of disease progression).

* Tissue : RNAseq will be performed on tumor biopsy (10 slides of 5 microns) to identify the ALK fusion partner and its variant and associated co-mutations.. * ctDNA : NGS panel on DNA including a large panel of fusions and mutations will be performed on blood samples (30mL on EDTA or STRECKs tubes) at diagnosis, at the time of the first evaluation and at the time of progression).

For plasma testing, after obtained patient consent, blood samples (35mL on EDTA or STRECKs tubes) at diagnosis, at the first evaluation and at disease progression will be taken.

The ALKis include alectinib and brigatinib as first-line therapy or other drugs with marketing authorizations (lorlatinib, entrectinib) or in early access programs (EAPs).

Liquid biopsies will be analyzed with a NGS panel allowing the identification of ALK fusion partners and resistance mechanisms (mutations, fusions, copy number variations). Samples will be sent for centralized analysis to the Léon Bérard Center (Lyon).

For biological analysis on tissue obtained at diagnosis, the ALK fusion partner and its variant will be identified by RNAseq. Whenever a tissue re-biopsy is performed at the time of disease progression as part of the standard of care management of the patient, the remaining tissue sample will be collected as part of the BioExALK study, so that RNAseq analysis will be performed to look for resistance mechanisms. Tissue samples (10 slides of 5 microns) will be sent for centralized analysis to the Rouen University Hospital.

• Overall Survival (OS) [Срок оценки: From date of treatment initiation up to 72 months]
• Duration of Response (DoR) [Срок оценки: From date of treatment initiation up to 72 months]
• Overall Response Rate (ORR) [Срок оценки: From date of treatment initiation up to 72 months]
• Circulating tumoral DNA (ctDNA) clearance on Progression Free Survival (PFS) of stage IV ALK-rearranged NSCLC patients [Срок оценки: From date of treatment initiation up to 72 months]
• Circulating tumoral DNA (ctDNA) clearance on Overall Survival (OS) of stage IV ALK-rearranged NSCLC patients [Срок оценки: From date of treatment initiation up to 72 months]
• Circulating tumoral DNA (ctDNA) clearance on Duration of Response (DoR) of stage IV ALK-rearranged NSCLC patients [Срок оценки: From date of treatment initiation up to 72 months]
• Circulating tumoral DNA (ctDNA) clearance on Overall Response Rate (ORR) of stage IV ALK-rearranged NSCLC patients [Срок оценки: From date of treatment initiation up to 72 months]
• Description of mechanisms of resistance associated with first-line tyrosine kinase inhibitors [Срок оценки: From date of treatment initiation up to 72 months]
• Description of mechanism of resistance associated with each ALK-fusion partner [Срок оценки: From date of treatment initiation up to 72 months]
• Concordance between ALK fusion partner and co-mutations [Срок оценки: From date of treatment initiation up to 72 months]
• Impact of presence or absence of serum Anti-ALK antibodies at diagnosis on OS [Срок оценки: From date of treatment initiation up to 72 months]