Clinical trial NCT06247826: Mechanisms of Resistance to Amivantamab in Patients With NSCLC With EGFR Exon 20 Insertion
Official title: Mechanisms of Resistance to Amivantamab in Patients With NSCLC With EGFR Exon 20 Insertion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non-small Cell Lung Cancer
EGFR Exon 20 Insertion Mutation
Lead sponsor: Groupe Francais De Pneumo-Cancerologie
Sponsor class: OTHER
First posted: 2024-02-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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 outcomes:
measure: Percentage of molecular alterations
timeFrame: At disease progression on a period up to 18 months at maximum
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 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
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Oncologie Polyclinique Bordeaux Nord Aquitaine
city: Brest
country: France
facility: Centre Hospitalier du Morvan
city: Creteil
country: France
facility: Pneumologie Centre Hospitalier Intercommunal de Créteil
city: Dijon
country: France
facility: Oncologie, CLCC Dijon
city: Grenoble
country: France
facility: Pneumologie, CHU Grenoble
city: Le Mans
country: France
facility: Pneumologie CH
city: Marseille
country: France
facility: Oncologie thoracique Hôpital Nord
city: Nice
country: France
facility: Oncologie, Centre Antoine Lacassagne
city: Paris
country: France
facility: Oncologie Institut Curie
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Pneumologie, Hôpital Tenon
city: Pau
country: France
facility: Pneumologie Centre Hospitalier
city: Quimper
country: France
facility: Pneumologie CHI Cornouaille
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Saint-Denis
country: France
facility: CHU La Réunion Site Nord
city: Saint-Étienne
country: France
facility: CHU Hôpital Nord
city: Vannes
country: France
facility: CH Bretagne Atlantique
city: Villeurbanne
country: France
facility: Pneumologie, Hôpital Mutualiste Resamut
Study officials:
affiliation: Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques Hôpital Nord-APHM
name: Pascale Tomasini
role: PRINCIPAL_INVESTIGATOR
affiliation: Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques Hôpital Nord-APHM
name: Maude Dupé-Pelletier
role: PRINCIPAL_INVESTIGATOR
References: