MedPath

Mechanisms of Resistance to Amivantamab in Patients With NSCLC With EGFR Exon 20 Insertion

Not Applicable
Recruiting
Conditions
Non-small Cell Lung Cancer
EGFR Exon 20 Insertion Mutation
Interventions
Procedure: Blood sampling
Registration Number
NCT06247826
Lead Sponsor
Groupe Francais De Pneumo-Cancerologie
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Experimental armBlood samplingPatients presenting advanced NSCLC with EGFR ins20 already treated with amivantamab as monotherapy in France under Temporary Use Authorisation or Early Access Program who will accept to provide blood samples at disease progression.
Primary Outcome Measures
NameTimeMethod
Percentage of molecular alterationsAt 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 Outcome Measures
NameTimeMethod
Progression Free SurvivalFrom 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.

Trial Locations

Locations (18)

Pneumologie, Hôpital Tenon

🇫🇷

Paris, France

Oncologie Polyclinique Bordeaux Nord Aquitaine

🇫🇷

Bordeaux, France

Centre Hospitalier du Morvan

🇫🇷

Brest, France

Pneumologie Centre Hospitalier Intercommunal de Créteil

🇫🇷

Creteil, France

Oncologie, CLCC Dijon

🇫🇷

Dijon, France

Pneumologie, CHU Grenoble

🇫🇷

Grenoble, France

Oncologie thoracique Hôpital Nord

🇫🇷

Marseille, France

Oncologie Institut Curie

🇫🇷

Paris, France

Pneumologie CH

🇫🇷

Le Mans, France

Oncologie, Centre Antoine Lacassagne

🇫🇷

Nice, France

Hôpital Cochin

🇫🇷

Paris, France

Pneumologie Centre Hospitalier

🇫🇷

Pau, France

Hôpital Charles Nicolle

🇫🇷

Rouen, France

Pneumologie CHI Cornouaille

🇫🇷

Quimper, France

CH Bretagne Atlantique

🇫🇷

Vannes, France

CHU La Réunion Site Nord

🇫🇷

Saint-Denis, France

CHU Hôpital Nord

🇫🇷

Saint-Étienne, France

Pneumologie, Hôpital Mutualiste Resamut

🇫🇷

Villeurbanne, France

© Copyright 2025. All Rights Reserved by MedPath