A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.

Inclusion Criteria:

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