Induction of Sensecence Using Dexamethasone to Re-sensitize NSCLC to Anti-PD1 Therapy

Inclusion Criteria:

* Be willing and able to provide written informed consent/assent for the trial.
* Be 18 years of age on day of signing informed consent.
* Have a life expectancy of at least 6 months.
* Have a histologically confirmed diagnosis of stage IV NSCLC (includes patients who have progressed on durvalumab for Stage III NSCLC) and have at least one measurable lesion based on RECIST v1.1.
* Have a performance status of 0, 1 or 2 on the ECOG Performance Scale (Appendix 15.1).
* Demonstrate adequate organ function all screening labs should be performed within 14 days of enrollment.
* Female subject of childbearing potential should have a serum pregnancy within 14 days of enrollment and 72 hours prior to receiving the first dose of study medications.
* Female subjects of childbearing potential must be willing to use a highly effective method of contraception as outlined in Section 6.3.3 for the course of the study through 180 days after the last dose of study medications.

  * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
* Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 180 days after the last dose of study therapy.

  * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
* Adequate tissue sample for correlative studies. A new sample is not necessary if archival specimen is available and has adequate amount of tumor content (at least 30%). This needs to be determined by a pathologist.

Exclusion Criteria:

* Received palliative radiation within 7 days of enrollment.
* Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.

  * Note: the time requirement for no evidence of disease for 5 years does not apply to the NSCLC tumor for which a subject is enrolled in the study. The time requirement also does not apply to subjects who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to enrollment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior enrollment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
* Has active autoimmune disease that has required systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

  * Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Subjects requiring daily corticosteroids \>10mg of prednisone (or its equivalent) would be excluded from the study.

  * Note: Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would NOT be excluded from the study.
* Has evidence of interstitial lung disease or a history of non-infectious pneumonitis that required oral or intravenous glucocorticoids to assist with management.

  * Note: Lymphangitic spread of the NSCLC is not exclusionary.
* Has an active infection requiring systemic therapy.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Subjects with cognitive functioning/impairment based on medical record review ad physician decision.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment.
* Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency (AIDS)-related illness) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
* Has a known history of active TB (Bacillus Tuberculosis).
* Has known active Hepatitis B or Hepatitis C.
* Has received a live vaccine within 30 days of enrollment.

  * 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.
* BASELINE CORTICOSTEROID AT STUDY ENTRY - subjects may not be on any steroids (dexamethasone, prednisone, etc) at the time of consent/study start.