This phase Ib study will investigate dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of afatinib and ruxolitinib combination therapy, based on the preclinical data that inhibition of IL-6R/JAK1 signal transmission pathway will increase sensitivity to afatinib.

Inclusion Criteria:

1. Stage 4 NSCLC patients
2. disease progression after platinum doublet (all), EGFR TKI (if EGFR mutant), and crizotinib (if ALK positive)
3. Men and women aged 20 years or older
4. Recovery from previous drug-related toxicity: CTCAE 4.03 ≤ Grade 1
5. ECOG 0 or 1
6. able to orally take and retain drug
7. have a measurable or unmeasurable lesion under RECIST 1.1 Criteria
8. have proper hematological, renal, and hepatic functions
9. intention to use an acceptable contraception
10. able to read and understand the informed consent form

Exclusion Criteria:

1. previous chemotherapy, radiation therapy, immunotherapy, or other anticancer therapy within 14 days
2. Clinically significant gastrointestinal disorder or malabsorption syndrome
3. Acute digestive disorder
4. major organ failure
5. Significant cardiac disorders
6. major operation of a main organ in 4 weeks
7. Untreated symptomatic brain metastasis
8. pregnant or nursing
9. previously diagnosed Interstitial lung disease(ILD)
10. previously treated with irreversible pan-HER inhibitor including Afatinib or Ruxolitinib
11. previously experienced hypersensitivity to an ingredient of the study drug
12. must receive CYP3A4 inducer or inhibitor persistently during the study period.
13. HIV positive or active hepatitis
14. threatening patient's safety is predicted