MEchanisms of Resistance in EGFR Mutated Nonpretreated Advanced Lung Cancer Receiving OSimErtib
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03865511
- Lead Sponsor
- Nantes University Hospital
- Brief Summary
Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer.
The AURA 3 study (T790M-positive advanced non-small-cell lung cancer in progression after first-line EGFR-TKI therapy, shown that the median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months p\<0.001).
In addition, clinical data show that patients with mutated EGFR NSCLC receiving osimertinib in first line, presented an objective response rate of 77 % with a disease control rate of 98 % and a median PFS was 19.3 months.
Finally, The FLAURA study randomized phase 3 study clearly demonstrated the superiority of osimertinib compared with erlotinib or gefitinib in EGFR mutated nonpretreated NSCLC (median PFS of 18.9 months versus 10.2 months).
However, several issues remain unknown or debated :
* What are the mechanisms of resistance to osimertinib prescribed in first-line?
* What are the consequences of prolonged exposure to osimertinib on the expression of markers of response to immunotherapy?
* Is there an association between kinetic parameters of ctDNA (circulating tumor DNA) and prediction of response to osimertinib and/ or and prediction of therapeutic escape under osimertinib? In order to respond to all these questions, this phase II trial will be the first to systemically analyze the mechanisms of resistance to Osimertinib based on the analysis of biopsy, and collection of plasma from all patients during the course of treatment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 150
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TAGRISSO® 80mg (Osimertinib) TAGRISSO® 80mg (Osimertinib) Oral administration of TAGRISSO® 80mg (Osimertinib) as a single daily dose until disease progression or unacceptable toxicity. Tumor biopsies performed at baseline and clinical progression. ctDNA analysis by Collection of plasma (two 10-ml Streck tubes) at each time point indicated in the trial. TAGRISSO® 80mg (Osimertinib) Tumor biopsies Oral administration of TAGRISSO® 80mg (Osimertinib) as a single daily dose until disease progression or unacceptable toxicity. Tumor biopsies performed at baseline and clinical progression. ctDNA analysis by Collection of plasma (two 10-ml Streck tubes) at each time point indicated in the trial. TAGRISSO® 80mg (Osimertinib) ctDNA analysis Oral administration of TAGRISSO® 80mg (Osimertinib) as a single daily dose until disease progression or unacceptable toxicity. Tumor biopsies performed at baseline and clinical progression. ctDNA analysis by Collection of plasma (two 10-ml Streck tubes) at each time point indicated in the trial.
- Primary Outcome Measures
Name Time Method Examination of the genetic profile at the point of disease progression in EGFRm+ (mutated Epidermal Growth Factor Receptor) patients receiving osimertinib as first-line EGFR TKI therapy compared to baseline. At clinical disease progression (approximately 22 months) Analyze of the proportion of patients with a given genetic marker on tumor biopsy (including, but not limited to, EGFR mutations, HER2 (Human Epidermal Growth factor receptor 2), and cMET expression and/or amplification) at the point of clinical disease progression.
- Secondary Outcome Measures
Name Time Method Clinical objective : To assess efficacy of Osimertinib every 3 months until radiological disease progression (approximately 22 months) Objective Response Rate (ORR)
Clinical objective : To assess efficacy of Osimertinib: Duration of Response (DoR): Disease Control Rate (DCR) every 3 months until radiological disease progression (approximately 22 months) Duration of Response (DoR): Disease Control Rate (DCR)
Clinical objective : To assess safety of Osimertinib with Monitoring of Adverse events (grade 3 and 4) monthly from first study dose until 15 days after last study dose Monitoring of Adverse events (grade 3 and 4)
Biological objective : To evaluate diagnostic accuracy of ctDNA to detect mutation At baseline and monthly until clinical disease progression (approximately 22 months) Analyze of mutation at progression on tumor tissue and ctDNA
Biological objective : To compare the genetic profile of the ctDNA and the tumor biopsy At baseline and at clinical disease progression (approximately 22 months) Analyze of the EGFR mutation identified in the tumor biopsy and in the ctDNA
Biological objective : To evaluate the consequence of osimertinib treatment on the expression of targets of immune check point inhibitors At baseline and at clinical disease progression (approximately 22 months) By the study of the expression of molecules involved in the efficacy of check point inhibitors determined by immunohistochemistry (PD-L1; CD73; CD4; CD8) on tumor tissue collected at progression
Biological objective : To demonstrate that the early kinetics of ctDNA is an indicator of response to osimertinib At baseline and monthly until clinical disease progression (approximately 22 months) Analyze of absolute quantities of ctDNA molecules presenting the EGFR mutation identified in the tumor, clinical progression disease
Biological objective : To observe if the presence of ctDNA at baseline is a prognostic factor of clinical progression disease At baseline and monthly until clinical disease progression (approximately 22 months) Analyze of the presence of tumors ctDNA at baseline, clinical progression disease
Biological objective : To measure the biological progression (bPFS) in patients treated with osimertinib At baseline and monthly until clinical disease progression (approximately 22 months) Serial monitoring in ctDNA of molecular alterations identified in tissues collected at progression
Biological objective : To compare the kinetic of appearance of EGFR mutation and radiological and clinical progression disease At baseline and monthly until clinical disease progression (approximately 22 months) Analyze of the absolute quantities of ctDNA molecules presenting the EGFR mutation monthly, radiological and clinical progression disease
Trial Locations
- Locations (17)
Hôpital Calmette CHRU de Lille
🇫🇷Lille, France
CH de Cholet
🇫🇷Cholet, France
C H I Créteil
🇫🇷Créteil, France
CH Le Mans
🇫🇷Le Mans, France
Chru Strasbourg
🇫🇷Strasbourg, France
Chu Tours
🇫🇷Tours, France
CHU d'ANGERS
🇫🇷Angers, France
Chu Grenoble
🇫🇷La Tronche, France
Chru Pontchaillou
🇫🇷Rennes, France
Crlcc Francois Baclesse
🇫🇷Caen, France
CHD Vendée
🇫🇷La Roche-sur-Yon, France
AP-HM Hôpital Nord Marseille
🇫🇷Marseille, France
CHU de Nantes
🇫🇷Nantes, France
Chits Ch Sainte Musse
🇫🇷Toulon, France
CH DU MOENCHSBERG - Hôpital Emile Muller
🇫🇷Mulhouse, France
Institut Curie
🇫🇷Paris, France
AP-HP Hôpital Tenon
🇫🇷Paris, France