Phase Ib/II Clinical Trial Evaluating the Safety and Efficacy of Chemoimmunotherapy Plus Short Course of Mek Inhibitor in First Line of Treatment of Metastatic Non Squamous Non Small Cell Lung Adenocarcinoma With PDL1 < 50 %.
Monocentric study composed by 2 steps : 1. First step is a phase I with the aim of establish the recommended dose of mirdametinib administration (2 or 4 mg twice a day for 7 or 14 days per cycle for the 4 first of carboplatin/pemetrexed/pembrolizumab treatment) 2. Second step is a non comparative randomized (2:1) phase II trial testing the recommended dose of mirdametinib administration. The aim is the efficacy and safety of short course of mirdametinib treatment for the 4 first cycles of the carboplatin/pemetrexed/pembrolizumab treatment.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Patients must be diagnosed with a metastatic or locally advanced non squamous non-small cell lung cancer
• Absence of previous treatment for or locally advanced or metastatic non-small cell lung cancer. Previous adjuvant therapy is allowed if \> 12 months from the last injection
• Age \>18 years at time of study entry
• Performance status ECOG of 0 or 1
• Life expectancy ≥ 6 months
• PD-L1\<50% using TPS scoring
• At least one lesion measurable as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1) that can be accurately assessed at baseline and is suitable for repeated assessment
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below:
• Adequate cardiac function:
⁃ (QTc \< 450 msec on baseline ECG, using the Fridericia correction cQTcF formula) or other clinically significant ventricular or atrial arrhythmia.
⁃ Left ventricular ejection fraction (LVEF) ≥ 50%
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Patient affiliated to a social security regimen or beneficiary of the same according
• Validation of the quality and quantity of the tumoral material at inclusion (existing material dated less than one month and/or fresh biopsy).
• Patient is willing to perform the fresh biopsies mandatory for the protocol:
⁃ Phase I: A mandatory fresh biopsy of 4 samples at inclusion and after Cycle 2 (betweenC2J7 and C2J14) Phase II: A mandatory fresh biopsy. of 4 samples at inclusion. Second biopsy at 4-5 weeks after treatment initiation is optional.