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 6
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 6 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

- QTc>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