This early phase I trial studies how well dacomitinib with or without osimertinib works in treating patients EGFR mutant lung cancers that has spread to other places in the body (metastatic) and has progressed after treatment with osimertinib. Dacomitinib and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03755102.
PRIMARY OBJECTIVES:
I. To provide preliminary estimates of the overall response rate (partial and complete responses) of dacomitinib in patients with EGFR-mutant lung cancers and disease progression on osimertinib.
II. To provide preliminary estimates of the overall response rate (partial and complete responses) of dacomitinib + osimertinib in patients with EGFR-mutant lung cancers and disease progression on osimertinib.
SECONDARY OBJECTIVES:
I. Measure progression-free survival (PFS).
II. Measure overall survival (OS).
CORRELATIVE OBJECTIVES:
I. Identify any pre-treatment biomarkers that predict response to dacomitinib with or without osimertinib in this setting (EGFR C797S or other).
II. Identify molecular biomarkers within plasma (sensitizing EGFR mutation, EGFR C797S, EGFR T790M), quantify and follow serially over time.
III. Determine the mechanisms of resistance to dacomitinib with or without osimertinib treatment.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I (CLOSED TO ACCRUAL): Patients receive dacomitinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive dacomitinib PO QD and osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then periodically thereafter.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorHelena A. Yu
