Understanding and Overcoming the Early Adaptive Resistance to EGFR Tyrosine-kinase Inhibitors in Lung Cancer Patients (LUNG-RESIST)

  • End date
    Jan 23, 2023
  • participants needed
  • sponsor
    University Hospital, Toulouse
Updated on 23 May 2022
growth factor
epidermal growth factor receptor
cancer chemotherapy
epidermal growth factor
advanced lung cancer
lung carcinoma


Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) are effective therapies for advanced lung cancer patients bearing EGFR-activating mutations, but are not curative due to the invariable apparition of resistances. The investigator team have identified a new phenotype related to drug tolerance after EGFR-TKI treatment that shares several characteristics of a known process of Therapy-Induced Senescence (TIS), which could be a major event of drug tolerance in patients. Using cutting-edge technologies, patient-derived xenografts (PDX) and circulating tumor cells (CTC), the investigator team will perform an exhaustive characterization of the phenotypic and molecular changes associated with this drug-tolerant state in patients. Their results should lead to new therapeutic approaches to eliminate the reservoir of drug-tolerant cells and to prevent emergence of resistance mutations responsible for the relapse of patients.


LUNG-RESIST is a translational, monocentric and prospective research study on 40 patients whose objective is to characterize Drug Tolerant Cell (DTC) type cells in patients with a NSCLC carrying an EGFR mutation and to discover and monitor potentials biomarkers involved in this mechanism of resistance to osimertinib. The study will be offered to patients, and for whom the therapeutic decision was decided collegially during multidisciplinary molecular meetings (molecular Tumor Board). Following informed consent, patients will be registered in a single cohort. In this study, treatment with osimertinib is not studied and will be delivered according to current recommendations

Condition Lung Cancer, Nonsmall Cell
Treatment blood samples
Clinical Study IdentifierNCT04222335
SponsorUniversity Hospital, Toulouse
Last Modified on23 May 2022


Yes No Not Sure

Inclusion Criteria

Patient with non operable and / or metastatic non-small cell lung cancer documented histologically
Pathological diagnosis of NSCLC carrying an EGFR activating mutation associated with sensitivity to the tyrosine kinase inhibitors (TKI) (exons 18, 19 and 21)
Sufficient tissue sample quantity and quality for translational research
Naïve TKI-treated EGFR patient who can receive first-line treatment with Osimertinib or second-line after chemotherapy

Exclusion Criteria

Any patient with an exon 20 EGFR mutation
Any disease or pathology that recommend not to perform blood samples collection
Any psychological, family, geographical or social condition that could potentially, according to the investigator's judgment, prevent the collection of informed consent or interfere with compliance with the study protocol
Patient with a resistance mutation of EGFR
Patient under State Medical Assistance
Patient deprived of liberty on administrative or judicial decision, or patient under guardianship, curatorship or safeguard of justice
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