Slow enrollment.

This is a research study to find out the safety and tolerability of combining the drug evolucumab with standard immunotherapy in people with advanced lung cancer (a type called non-small cell lung cancer).

Nivolumab (Opdivo™) and ipilimumab (Yervoy™) are immunotherapy-type drugs which are approved for the treatment of advanced lung cancer that has expression of PD-L1 greater than or equal to 1%. Evolucumab is being combined with nivolumab and ipilimumab to see if it will improve the anti-tumor capabilities of the immunotherapy. Adding evolocumab to the combination of nivolumab and ipilimumab has not been tested in people before and is considered investigational.

Inclusion Criteria:

1. All patients must have histologically documented or suspected recurrent incurable and/or stage 4 squamous or non-squamous NSCLC.
2. NO prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis recurrent/metastatic NSCLC. Medical therapy (including adjuvant or maintenance immune therapy) for early stage NSCLC allowed if completed > 6 months prior to study enrollment.
3. TPS PD-L1 < 50%
4. Performance Status ECOG 0-1 (Appendix B).
5. Age >18 years old.
6. No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive.
7. No autoimmune disease that would constitute contraindication to receive nivolumab
8. Patients must have core needle biopsy tissue that is available and adequate for dedicated research purposes.
9. No excessive risk for CT or ultrasound guided percutaneous biopsy to obtain research biopsy specimen. Risk assessment is to be determined by the treating oncologist and the interventional radiologist.
10. Patients who do not have an indication for a diagnostic biopsy must undergo an elective 'research only' core needle biopsy.
11. Signed written informed consent including HIPAA according to institutional guidelines.
12. Safety laboratory values within institutional normal ranges.

Exclusion Criteria:

• 1) Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

  2) Has a known history of active TB (Bacillus Tuberculosis) 3) Hypersensitivity to nivolumab or ipilimumab or any of its excipients 4) Hypersensitivity to evolocumab or any of its excipients 5) Patient does not have a site of suspected malignancy that is accessible to pre-treatment biopsy.

  6) Concurrent administration of any other anti-tumor therapy. 7) Has received prior therapy with a PD1, PDL1, or PDL2 inhibitor. 8) Has received therapy with PCSK9 inhibitor within 90 days of study entry. 9) Known active CNS metastases which are symptomatic. Eligible if metastases have been locally treated 14 days prior to cycle 1 day 1, are clinically controlled, and asymptomatic off high dose steroids on cycle 1 day 1(< 2 mg decadron or 10 mg prednisone daily or equivalent allowed). Untreated, asymptomatic brain metastases allowed if subject does not require corticosteroids or anticonvulsant therapy.

  10) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

  11) Inability to comply with protocol or study procedures. 12) Active infection requiring antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.

  13) Has known history of, or any evidence of active, non-infectious pneumonitis.

  14) Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) 15) Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc) is not considered a form of system treatment. Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).

  16) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity 17) Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

  18) Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

  19) Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant disorders that in the opinion of the investigator would compromise the safety of the patient of compromise the patient's ability to complete the study.

  20) Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 30 days before or after any dose of nivolumab). Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed. COVID19 vaccines will be allowed on protocol.

  21) Myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications. Patients with CAD recently treated with surgery and/or stent, if stable without symptomatic angina pectoris, active ischemia are eligible.

  22) Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

  23) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either psychiatric or physical (e.g., infectious) illness.

  24) Patient takes daily prednisone > 10 mg or the equivalent dose of a different steroid.

Up to 2 years