A Study of the Combination of Osimertinib, Platinum and Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers

Inclusion Criteria:

Written informed consent
Advanced biopsy-proven metastatic non-small cell lung cancer
Either have not started an EGFR TKI or may have started osimertinib within the last 9 weeks
Somatic activating mutation in EGFR in pre-treatment tumor biopsy or cfDNA
Evidence of a concurrent P53 alteration by IHC or NGS on pre-treatment tumor biopsy or cfDNA
Evidence of a concurrent RB1 alteration by IHC or NGS on pre-treatment tumor biopsy or cfDNA
Must have a site of disease amenable to repeat biopsy and be willing to undergo a biopsy during treatment
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 ≤ 3 x ULN
Total bilirubin ≤ 1.5x ULN
Creatinine ≤ 1.5x ULN OR calculated creatinine clearance ≥ 60ml/min
Absolute neutrophil count (ANC) ≥ 1000 cells/mm^3
Hemoglobin≥8.0 g/dL
Platelets ≥100,000/mm^3

Exclusion Criteria:

Pregnant or lactating women
Started an EGFR TKI other than osimertinib or started osimertinib more than 9 weeks ago
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
Have pure small cell histology
Corrected QT interval using Fridericia's formula (QTcF)>475msec or any clinically significant (as deemed by the investigator) abnormalities in rhythm or conduction or morphology of the resting EKG.
Patients are to be excluded from cisplatin treatment arm if they meet any of the following criteria:
Creatinine clearance < 60 ml/min
Hearing impairment requiring assistive device
Neuropathy
The treating provider does not feel as though the patient should receive cisplatin