This phase Ib trial evaluates the best dose and side effects of MRX-2843 when given in combination with osimertinib in treating patients with EGFR gene mutant non-small cell lung cancer that has spread to other places in the body (advanced). MRX-2843 and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Patients must have histologically confirmed metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation including typical and atypical mutations in egfr exons 19 and 21
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Patients in the expansion cohort must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
Ability to safely swallow oral medication
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1)
Patients who are receiving any other investigational agents
Patients with symptomatic untreated brain metastases would be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patient with treated or asymptomatic untreated brain metastasis is allowed on study
Single group
Flt3/MerTK Inhibitor MRX-2843
DrugGiven PO
Osimertinib
DrugGiven PO
Maximum tolerated dose (MTD)
The computation of the dose to be administered to each patient and the 95% highest posterior density credible interval estimate of the MTD will be carried out using computer program escalation with overdose control (EWOC) version 3.1 and R. Upon completion of the trial, the MTD will be estimated as the median of the marginal posterior distribution of the MTD.
Recommended phase 2 dose (RP2D) of the tested combination (dose escalation)
The highest dose level of the combination that is under-toxic and safely tolerated would be considered the RP2D.
Predictive Protein Biomarkers
Change in the level of expression of biomarkers of interest (phosphorylated and total EGFR)
Predictive Protein Biomarkers
Change in the level of expression of biomarkers of interest (phosphorylated and total MERTK)
Overall response rate (ORR) (dose expansion)
All patients included in the study will be assessed for response to treatment, even if there are major protocol treatment deviations or if they are ineligible.One sample exact binomial test, and logistics regression will be used to test the ORR in the osimertinib resistant cohort.
1-year progression free survival rate (dose expansion)
Will be assessed using Kaplan Meier method, log-rank test, and Cox model in the osimertinib naive cohort.
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Emory University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
