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

Non-small Cell Lung Cancer Clinical Trial

— RESAMEX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06247826
• Other study ID #: GFPC 06-2023
• Status: Recruiting
• Phase: N/A
• Start date: January 15, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: January 2024
• Source: Groupe Francais De Pneumo-Cancerologie
• Contact: Laurent GRELLIER
• Phone: +33 (0)4 91 96 59 01
• Email: laurent.greillier[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Procedure:
• Blood 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.

Locations

Country	Name	City	State
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	Pneumologie CH	Le Mans
France	Oncologie thoracique Hôpital Nord	Marseille
France	Oncologie, Centre Antoine Lacassagne	Nice
France	Hôpital Cochin	Paris
France	Oncologie Institut Curie	Paris
France	Pneumologie, Hôpital Tenon	Paris
France	Pneumologie Centre Hospitalier	Pau
France	Pneumologie CHI Cornouaille	Quimper
France	Hôpital Charles Nicolle	Rouen
France	CHU La Réunion Site Nord	Saint-Denis
France	CHU Hôpital Nord	Saint-Étienne
France	CH Bretagne Atlantique	Vannes
France	Pneumologie, Hôpital Mutualiste Resamut	Villeurbanne

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Francais De Pneumo-Cancerologie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of molecular alterations	Percentage of molecular alterations found at the time of disease progression on amivantamab monotherapy in patients with advanced NSCLC with EGFR ins20.	At disease progression on a period up to 18 months at maximum
Secondary	Progression Free Survival	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.	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