Phase I/II Study of Lenalidomide Plus Pembrolizumab in Patients With Solid Tumors With Expansion in Non-small Cell Lung Cancer

Inclusion Criteria: 1. Patients must have a histologically or cytologically confirmed metastatic solid tumor malignancy for the phase I component. The phase II component will require patients to have histologically or cytologically confirmed non-small cell lung carcinoma regardless of histology. 2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1. 3. For participation in the Phase II portion, patients must have completed at least one line of prior therapy. For participation in the Phase I portion, patients must have completed either one or two lines of prior therapy. 4. Treatment on this protocol may begin as long as the patient has recovered from toxicities of prior therapy at the discretion of the treating physician. Patients with NSCLC harboring an EGFR, ALK or ROS-1 alteration must have progressed through at least one prior therapy with appropriate molecularly targeted agents. 5. Age \> 18 years. 6. ECOG performance status 0 or 1. 7. Patients must have normal organ and marrow function 8. Ability to understand and willingness to sign a written informed consent and HIPAA consent document. 9. Palliative radiation for treatment of painful bone metastasis, control of hemoptysis or treatment of small asymptomatic brain metastasis that become symptomatic during on protocol treatment is allowed. Protocol treatment will be delayed until recovery from radiation at the discretion of the treating physician. 10. A core tumor biopsy obtained after progression on the last treatment must be available at study entry for the phase II portion of the study. Any available archival tissue (for both phase I and II) will also be collected. 11. Female subject of childbearing potential must have a negative serum pregnancy 10-14 days prior to registration, and again within 24 hours prior to the first dose of Lenalidomide,. 12. Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. 13. Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 14. Ten patients with a diagnosis of NSCLC who have disease progression per investigator's assessment who are on anti PD-1 or PD-L1 therapies will be allowed to enroll in the phase II part of this study but must be switched to treatment per this protocol. Exclusion Criteria: 1. Patients who have had chemotherapy or radiotherapy within14 days prior to entering the study. Patients may not be currently receiving any other investigational agents or immunomodulatory agents (e.g. ipilimumab). Patients treated with prior PD-1 or PD-L1 directed therapies are ineligible for the phase I portion. 2. Patients who, at the discretion of the treating physician, have not recovered from adverse events due to agents administered earlier. 3. Patients with 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 4. Patients with untreated symptomatic brain metastases. Patients with treated brain metastases will be allowed if brain imaging obtained within 30 days of trial enrollment reveals stable disease. Patients with small asymptomatic brain metastasis are allowed to enroll. Patients on steroids doses higher than 10 mg of prednisone (or its equivalent) are excluded. 5. Patients with interstitial lung disease or active, noninfectious pneumonitis. 6. Patient who have received a live vaccine within 30 days prior to Cycle 1 Day 1. 7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including HIV, hepatitis B, hepatitis C), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements. 8. Patients with known hypersensitivity to thalidomide or lenalidomide or pomalidomide. 9. Patients with peripheral neuropathy of grade ≥3. Patients with painful grade 2 neuropathy are also excluded. 10. Pregnant or breast-feeding.