Inclusion Criteria:
1. Male or female subjects at least 18 years of age;
2. Ability to understand and the willingness to sign a written informed consent;
3. Histological or biopsy proven Non-Small Cell Lung Cancer (squamous or non-squamous);
4. ECOG performance status of 0-2;
5. Patients with evidence of:
* cancer cachexia, defined by the International Cancer Cachexia Consensus Definition (\>5% weight loss over the preceding 6 months prior to diagnosis); OR
* Patients with evidence of cancer pre-cachexia, defined by the International Cancer Cachexia Consensus Definition (0 to \<=5% weight loss over the preceding 6 months prior to diagnosis);
6. Any de novo stage IV NSCLC disease diagnosis as defined by AJCC 8th edition staging. Staged with PET/CT, MRI brain, or other acceptable staging tool; measurable disease as defined by RECIST 1.1;
7. Adequate end-organ function, based on routine clinical and laboratory workup and institutional guidelines, as determined by oncology team offering patient standard of care therapy, including:
1. ANC \>1,000 cells/µl, Platelets \> 100,000 cells/µl, Hemoglobin \> 10.0 g/dl;
2. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 45 ml/min;
3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN;
4. International normalized ratio (INR) (or prothrombin time (PT)) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, if values are within the intended therapeutic range;
8. Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: a. Has not undergone a hysterectomy or bilateral oophorectomy; or b. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months);
9. Male subjects who are surgically sterile or are using a medically acceptable form of contraception for 90 days following the completion of therapy;
10. Life expectancy anticipated to be 6 months or greater;
11. No prior therapy for advanced lung cancer.
Exclusion Criteria:
1. Subjects with confirmed stage I-III NSCLC;
2. Patients whose tumors have actionable mutations treatable with targeted therapies;
3. Patients with no evidence of cancer cachexia, defined by the International Cancer Cachexia Consensus Definition (\>5% weight loss over the preceding 6 months prior to diagnosis); OR Patients with no evidence of cancer pre-cachexia, defined by the International Cancer Cachexia Consensus Definition (0 to \<=5% weight loss over the preceding 6 months prior to diagnosis);
4. Active malignancy other than lung cancer that requires concurrent treatment other than hormonal therapy and is deemed by the treating physicians to be likely to affect the subject's survival duration;
5. Subjects who have not recovered or have disease control from prior treatment-related to toxicities judged by treating physician;
6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in study;
7. Uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements;
8. Inadequate liver or renal function, if out of the acceptable ranges of the inclusion criteria;
9. Significant bacterial, fungal, parasitic, or viral infection requiring treatment;
10. Previous treatment with a JAK inhibitor;
11. Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of ruxolitinib;
12. Females who are pregnant, breast-feeding or plan to become pregnant;
13. Participation in other clinical trials either to treat diagnosed lung or other cancers (patients on registry trials are eligible);
14. Requirement for treatment with drugs that may, in the judgment of the treating investigator, create a risk for a precipitous change in patient's health;
15. Any other conditions that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study;
16. Life expectancy of less than 6 months;
17. Prior therapy for the newly diagnosed advanced lung cancer.
18. Patients taking therapies that are strong CYP3A4 inhibitors and fluconazole.
