EGFR Exon 20 Insertion Mutation, Non-small Cell Lung Cancer
Conditions
Brief summary
The goal of this prospective, interventional study is to evaluate the mechanisms of acquired resistance to amivantamab monotherapy in patients with advanced NSCLC with EGFR ins20. The main question it aims to answer is: What are the mechanisms of acquired resistance to amivantamab monotherapy in this population of patients ? How anticipate the efficacy of subsequent systemic therapies ? After this information session, the participant will be asked to sign the study informed consent. A blood samples (2\*10 mL on ethylenediaminetetraacetic acid (EDTA)) will be taken at time of disease progression and will be sent for central liquid biopsy ctDNA analysis. If available, tumor tissue will also be sent for DNA NGS analysis.
Detailed description
RESAMEX is a prospective study evaluating the mechanisms of acquired resistance to amivantamab monotherapy in patients with advanced NSCLC with EGFR ins20. Biological analysis will be performed on circulating tumor deoxyribonucleic acid (ctDNA) at the time of disease progression and on tumor tissue at the time of disease progression when available. * ctDNA : The extraction of the ctDNA will be performed in an automated way with the Promega RSC LV cfDNA kit on Maxwell platform. Sequencing will be performed on NextSeq500 platform with a panel of 208 genes (including 190 genes with full coverage of coding regions, and 11 genes with coverage of introns involved in translocations) covering 800 kpb and at a target depth of 8000 X. * Tissue : Deoxyribonucleic acid (DNA) next generation sequencing (NGS) will be performed on tumor biopsy (10 slides of 5 microns) . Samples will be sent for centralized analysis to Centre de Recherche en Cancérologie de Marseille (CRCM), 27 Bd Lei Roure, 13009 Marseille (Prof. Tomasini and Gwenaël Lumet), and will be stored at Centre de Ressources Biologiques de l'Assistance Publique Hôpitaux de Marseille (CRB AP-HM), 264 Rue Saint-Pierre, 13005 Marseille.
Interventions
PROCEDUREBlood sampling
Blood samples (2\*10 mL on ethylenediaminetetraacetic acid (EDTA)) will be taken at time of disease progression and will be sent for central liquid biopsy ctDNA analysis.
Sponsors
Groupe Francais De Pneumo-Cancerologie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients with advanced NSCLC with EGFR ins20 receiving amivantamab as monotherapy in France under ATU or EAP; * Age ≥ 18 years; * Histologically confirmed advanced NSCLC (metastatic or locally advanced unresectable and not suitable for definitive radiotherapy) with EGFR ins20; * Patients included will be required to sign an informed consent form to collect blood samples (liquid biopsy) and tissue biopsy when available at progression on amivantamab; * Confirmed progression on amivantamab according to RECIST 1.1; * Patient enrolled in the french National Health Insurance program or with a third- party payer.
Exclusion criteria
* Patients receiving amivantamab in combination with another therapy; * Patients who do not consent to liquid biopsy at progression.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of molecular alterations | At disease progression on a period up to 18 months at maximum | Percentage of molecular alterations found at the time of disease progression on amivantamab monotherapy in patients with advanced NSCLC with EGFR ins20. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | From the date of first dose of treatment received until the date of the first documented disease progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 or to death from any cause, whichever came first, assessed up to 18 months | Progression free survival with the first subsequent therapy after amivatamab, defined as the time from first dose to first documentation of objective disease progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 or to death from any cause. |
Countries
France
Contacts
CONTACTLaurent GRELLIER
CONTACTSoizic Ferlandin
PRINCIPAL_INVESTIGATORPascale Tomasini
Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques Hôpital Nord-APHM
PRINCIPAL_INVESTIGATORMaude Dupé-Pelletier
Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques Hôpital Nord-APHM
Outcome results
None listed