A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.
Written informed consent Advanced biopsy-proven metastatic non-small cell lung cancer Somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy Prior treatment with osimertinib with response followed by disease progression No prior first or second generation EGFR inhibitor treatment (gefitinib, afatinib, erlotinib) Archival tissue available from a tumor biopsy done after disease progression on osimertinib or willing to undergo a tumor biopsy or liquid biopsy after disease progression on osimertinib prior to study initiation Measurable (RECIST 1.1) indicator lesion not previously irradiated Karnofsky performance status (KPS) >/= 70% Age >/= 18 years old Ability to swallow oral medication
Adequate organ function
AST, ALT Total bilirubin Creatinine /= 60ml/min Absolute neutrophil count (ANC) >/= 1000 cells/mm3 Hemoglobin>/=8.0 g/dL Platelets >/=75,000/mm3
Exclusion Criteria:
Pregnant or lactating women Any radiotherapy within 1 week of starting treatment on protocol. Any major surgery within 1 weeks of starting treatment on protocol. Any evidence of active clinically significant interstitial lung disease Continue to have unresolved > grade 1 toxicity from any previous treatment Treatment Patients with a known mechanism of resistance to osimertinib that will clearly not respond to dacomitinib therapy (i.e. known MET amplification, ALK fusion, RET fusion). Symptomatic brain metastases or leptomeningeal disease requiring escalating doses of steroids
