2024 World Conference on Lung Cancer (WCLC) - Posters-P1.12A.09 A Phase 1b Study of the MER Tyrosine Kinase Inhibitor, MRX-2843, in Combination with Osimertinib in Advanced EGFR Mutant Non-Small Cell Lung Cancer

P1.12A.09 A Phase 1b Study of the MER Tyrosine Kinase Inhibitor, MRX-2843, in Combination with Osimertinib in Advanced EGFR Mutant Non-Small Cell Lung Cancer

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The phase 1b study examines the combination of the MER tyrosine kinase inhibitor MRX-2843 with osimertinib for treating advanced EGFR mutant non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is effective initially, but resistance develops over time. MRX-2843, a small molecule inhibitor targeting the MERTK protein within the TAM kinase family, offers a potential strategy to combat such resistance. The study aimed to evaluate safety and efficacy for patients with EGFR mutant NSCLC.<br /><br />Participants were enrolled in dose-escalation cohorts to assess varying dosages of MRX-2843 (60mg to 160mg daily) combined with osimertinib (80mg daily). The escalation followed an overdose control design targeting 0.33 toxicity levels. Two dose-expansion cohorts included patients who were osimertinib-naive and those with resistance to it.<br /><br />Findings demonstrated that the combination was generally well tolerated, with most participants (65%) who had previously progressed on osimertinib alone experiencing stable disease or partial response. No dose-limiting toxicities (DLTs) were observed through dose levels 1-4 for MRX-2843. However, at the highest dose level (160mg), three patients experienced DLTs, including Grade 2 nausea/vomiting, Grade 4 hyponatremia, and Grade 3 pneumonitis, establishing this as the maximum tolerated dose (MTD) according to the escalation design.<br /><br />The study continues with dose expansion to further investigate the efficacy and safety profile of the MRX-2843 and osimertinib combination. With the clinical trial identification NCT #04762199, the initiative remains focused on understanding this treatment avenue's potential advantages in overcoming osimertinib resistance in EGFRm NSCLC.

Asset Subtitle

Conor Steuer

Meta Tag

Speaker Conor Steuer

Topic Metastatic NSCLC – Targeted Therapy

Keywords

MER tyrosine kinase inhibitor

MRX-2843

osimertinib

EGFR mutant NSCLC

non-small cell lung cancer

resistance

dose-escalation

toxicity

clinical trial

NCT04762199