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 %.

NCT05937906 | Recruiting Phase 1

• 1 other identifier: 2023-508477-87-00
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Monocentric study composed by 2 steps :

1. 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. 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.

Conditions

Non-Small Cell Lung Cancer

Keywords

locally advanced or metastatic; non squamous non small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Safety will be evaluated using Dose Limiting Toxicities (DLT)

  DLT is defined as any of the following toxicities occurring during the first 21 days after administration of the first dose. Adverse events (AEs) will be defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Until progression, an average of 10 months

Study Arms (6)

Phase I - Level 1

EXPERIMENTAL

Mirdametinib 4 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab. Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Drug: Phase I - Mirdametinib - Level 1

Phase I - Level 2

EXPERIMENTAL

Mirdametinib 4 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab. Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Drug: Phase I - Mirdametinib - Level 2

Phase I - Level 3

EXPERIMENTAL

Mirdametinib 6 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab. Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Drug: Phase I - Mirdametinib - Level 3

Phase I - Level 4

EXPERIMENTAL

Mirdametinib 6 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab. Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Drug: Phase I - Mirdametinib - Level 4

Phase II - Standard arm

NO INTERVENTION

Carboplatin / Pemetrexed / Pembrolizumab for the first 4 cycles

Phase II - Experimental arm

EXPERIMENTAL

Carboplatin / Pemetrexed / Pembrolizumab + mirdametinib for the first 4 cycles

Drug: Phase II - Mirdametinib

Interventions

Phase I - Mirdametinib - Level 1 DRUG

Mirdametinib 4 mg twice/day for 7 days per cycle

Phase I - Level 1

Phase II - Mirdametinib DRUG

For phase 2 : Randomisation with 2 arm : Standard arm and experimental arm

Phase II - Experimental arm

Phase I - Mirdametinib - Level 2 DRUG

Mirdametinib 4 mg twice/day for 14 days per cycle

Phase I - Level 2

Phase I - Mirdametinib - Level 3 DRUG

Mirdametinib 6 mg twice/day for 7 days per cycle

Phase I - Level 3

Phase I - Mirdametinib - Level 4 DRUG

Mirdametinib 6 mg twice/day for 14 days per cycle

Phase I - Level 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 2 months
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Presence of EGFR, ROS or ALK targetable mutations
• Major surgical procedure within 28 days prior to therapy initiation IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of study drug
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome).
• History of allogenic organ, bone marrow or double umbilical cord blood transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study physician Patients with celiac disease controlled by diet alone
• History of glaucoma, any retinal pathology considered to be a risk factor for central serous retinopathy, retinal vein occlusion (RVO) or neovascular macular degeneration. Also, any risk factors for RVO as intraocular pressure (IOP) \>21, uncontrolled blood glucose
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease. Any uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure (including history of myocardial infarction within 3 months, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or any cardiac arrhythmias, e.g, ventricular, supraventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening) uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high Resolution Computed Tomography (HRCT) sacan or any psychiatric disorder that prohibits obtaining informed consent.
• Currently taking medications with known risk of prolonging the QT interval or inducing Torsades de Pointes
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, cQTcF prolongation \>450ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML
• History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease
• History of leptomeningeal carcinomatosis

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead

Study Sites (1)

Centre Georges-François Leclerc

Dijon, Burgundy, 21000, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

François FG GHIRINGHELLI, Professor

CONTACT

0380737776; fghiringhelli@cgfl.fr

Emilie ER REDERSTORFF, Project manager

CONTACT

0345348116; erederstorff@cgfl.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Non applicable
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1 (escalation dose) * Level 1: mirdametinib 4 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients) * Level 2: mirdametinib 4 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients) * Level 3: mirdametinib 6 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients) * Level 4: mirdametinib 6 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients) Phase 2 (randomized) * Standard arm : Carboplatin/pemetrexed/pembrolizumab for the first 4 cycles until progression (26 patients) * Experimental arm : Carboplatin/pemetrexed/pembrolizumab + mirdametinib for the first 4 cycles until progression (52 patients)

Study Record Dates

• First Submitted: June 16, 2023
• First Posted: July 10, 2023
• Study Start: July 30, 2024
• Primary Completion (Estimated): May 25, 2028
• Study Completion (Estimated): May 25, 2028
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

FR (1)