This is a phase 2 study. The goal of this study is to find out what effects, good and/or bad, taking erlotinib and ruxolitinib has on the patients and on lung cancer. Erlotinib and ruxolitinib are FDA approved for other indications, but the use of erlotinib and ruxolitinib together has not been studied before and is not FDA-approved.

Inclusion Criteria:

• Pathologic evidence of advanced (non-operable or metastatic) biopsy-proven stage IV or recurrent lung cancer reviewed at MSKCC.

• a documented somatic activating mutation in EGFR (including but not limited to Exon 19 deletion or L858R)

• Radiographic progression during treatment with erlotinib. Prior chemotherapy regimens are permitted.

• Received erlotinib or other EGFR TK treatment for at least 2 weeks prior to enrollment

• Measurable (RECIST 1.1) indicator lesion not previously irradiated

• Must have undergone biopsy after development of acquired resistance to erlotinib (which is performed as standard of care) with adequate tissue to determine EGFR T790M and tumor histology. Slides from an outside institution may be used.

• KPS ≥ 70%

• Age>18 years old

• Patients must have adequate organ function:

  • AST, ALT, Alk phos ≤ 3.0 x ULN
  • Total bilirubin ≤ 2.0 x ULN
  • Creatinine <2.0 X upper limit of normal and/or a creatinine clearance ≥ 60ml/min
  • Absolute neutrophil count (ANC) ≥1,000 cells/mm³.
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9.0g/dL.

Exclusion Criteria:

• Concurrent therapy with a potent CYP3A4 inducer or inhibitor. Subjects may enter screening when therapy with the potent inhibitor or inducer is completed and may begin study treatment after 1 week or 5 half-lives, whichever is longer.
• Patients with symptomatic brain metastasis requiring escalating doses of steroids.
• Any type of systemic therapy (chemotherapy or experimental drugs) within 3 weeks of starting treatment on protocol except for erlotinib or other EGFR TKI.
• Any radiation within 2 weeks prior to starting treatment on protocol
• Patients with ≥ grade 2 or greater diarrhea despite maximal medical management due to medications or a medical condition such as Crohn's disease, malabsorption.
• Inadequate recovery from any toxicities related to prior treatment (to Grade 1 or baseline).
• Pregnant or lactating women
• Patients who have received prior treatment with JAK inhibitor
• Previously or current malignancies at other sites within the last 2 years, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, prostate cancer that does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines, superficial bladder cancer or other noninvasive indolent or stage 1 malignancy without sponsor approval.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, or symptomatic arrythmias requiring therapy,
• Chronic or current active infections requiring systemic antibiotics, antifungals or antiviral therapy.
• Known human immunodeficiency virus infection, or hepatitis B virus (HBV) viremia or hepatitis C virus (HCV) viremia. Screening for the study does not require assessment for these infections if not already known.
• Any other condition that, in the opinion of the Investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study.