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

ClinicalTrials.gov ID

NCT06247826

Lead Sponsor

Groupe Francais De Pneumo-CancerologieOTHER

Overall Status

Recruiting

Study Type

Interventional

Phase

Not Applicable

Enrollment

30Estimated

Last Update Posted

Apr 29, 2026Actual

Start Date

Jan 15, 2024Actual

Primary Completion Date

Jul 30, 2026Estimated

Completion Date

Jul 30, 2026Estimated

Official Title

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

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.

• Non-small Cell Lung Cancer
• EGFR Exon 20 Insertion Mutation

• Blood sampling

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Primary Purpose

Other

Allocation

N/A

Interventional Model

Single Group Assignment

Masking

None (Open Label)

Lead Sponsor

Groupe Francais De Pneumo-CancerologieOTHER

renaud.descourt@chu-brest.fr+33 298223827

lgalland@cgfl.fr

atoffart@chu-grenoble.fr

omolinier@ch-lemans.fr

pascale.tomasini@ap-hm.fr

elisa.gobbini@curie.fr

marie.wislez@aphp.fr

anthony.canellas@aphp.fr

also.renault@ch-pau.fr

michel.andré@ch-cornouaille.fr

florian.guisier@chu-rouen.fr

diane.moreau@chu-reunion.fr

sophie.bayle@chu-st-etienne.fr

gonzague.dechabot@ch-bretagne-atlantique.fr

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