NCT05937906

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 %.

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 %.

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Centre Georges Francois Leclerc · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

1\) Phase I (15-24 patients) Using a classical "3+3 design": The phase I will included a maximum 24 patients. 3 patients will be included in dose level 1, if not DLT occurs 3 patients will be included in level 2. If 1 DLT occurs 3 additional patients will be included; if 2 or more DLT occurs the trial will be stopped. At level 2 if no DLT occurs RP2D 3 patients will be included at level 3; If 1 DLT occurs 3 additional patients will be included; if 2 or more DLT occurs RP2D will be level 1. Similar rules will be applied for level 3 and 4. In absence of DLT CXCL10 and PD-L1, CD8 immune infiltrates and immunoscore IC (CD8-PDL1 dual markers) at baseline and 6 weeks, and clinical efficacy will be presented to IDMC for definition of RP2D. At the end of phase I inclusion toxicity, efficacy data and biological data (CXCL10 seric and IHC expression and PD-L1, CD8 immune infiltrates and immunoscore IC (CD8-PDL1 dual markers) at baseline and 6 weeks, PK and PK/PD data will be presented to IDMC to validate RP2D. * 3 +/- 3 patients for level 1 (mirdametinib 4 mg twice/ 7 days) * 3 +/- 3 patients for level 2 (mirdametinib 4 mg twice/ 14 days) * 3 +/- 3 patients for level 3 (mirdametinib 6 mg twice/ 7 days) * 3 +/- 3 patients for level 4 (mirdametinib 6 mg twice/ 14 days) PHASE II (78 patients) Sample size calculation was performed using PASS v13. In keynote 189 response rate in PD-L1 \<50% was 40% (28). A 3-month overall response rate (ORR) of 40% is considered unacceptable (P0=40%). The study team expect an ORR of 55% in the experiment arm (P1=55%, acceptable ORR). Using a single stage design (A Hern, exact test) with unilateral α=10%, power=80%, 50 patients are needed for the primary endpoint analysis in the experimental arm. With 5% of non-evaluable patients, 52 patients will be included in this arm. With a 2:1 randomization the control arm will include 26 patients. A total of 78 subjects are then needed in the phase 2 part.

Conditions

• Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Phase I - Mirdametinib - Level 1	Mirdametinib 4 mg twice/day for 7 days per cycle
DRUG	Phase II - Mirdametinib	For phase 2 : Randomisation with 2 arm : Standard arm and experimental arm
DRUG	Phase I - Mirdametinib - Level 2	Mirdametinib 4 mg twice/day for 14 days per cycle
DRUG	Phase I - Mirdametinib - Level 3	Mirdametinib 6 mg twice/day for 7 days per cycle
DRUG	Phase I - Mirdametinib - Level 4	Mirdametinib 6 mg twice/day for 14 days per cycle

Timeline

• Start date: 2024-07-30
• Primary completion: 2028-05-25
• Completion: 2028-05-25
• First posted: 2023-07-10
• Last updated: 2025-10-02

Locations

1 site across 1 country: France