TUSC2-nanoparticles and Erlotinib in Stage IV Lung Cancer

Inclusion Criteria: 1. Histologically or cytologically documented non-small cell lung cancer (NSCLC) 2. Stage IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy or surgery. There is no limit to the number or form of prior therapy regimens received, but patients must have received at least one. 3. All subjects must have tumor specimens adequate for analysis of EGFR mutations or have tumor accessible for pretreatment biopsy, and must consent to post-treatment Guardant ctDNA liquid biopsy. Subjects must have specimens adequate for analysis of EGFR mutations (and other clinically relevant biomarkers) 4. All subjects with an activating EGFR mutation (exon 19 deletion or exon 21 L858R mutation) are eligible IF they have progressed following treatment with a first, second, or third generation EGFR inhibitor. All subjects who are EGFR negative or have wild-type EGFR or another non-activating mutation are eligible. 5. ECOG or Zubrod Performance Status ≤1 6. Age ≥18 years 7. Subjects must have voluntarily signed an informed consent in accordance with institutional policies. 8. Female subjects of childbearing potential (non-childbearing is defined as greater than one year post-menopausal or surgically sterilized) must have a Negative serum pregnancy test (serum beta-HCG) ≤7 days of study treatment. Since beta-HCG may be falsely elevated as a result of malignancy, women of child-bearing potential who have an elevated serum beta-HCG level are eligible for enrollment if they have two (2) Transvaginal Ultrasound (TVUS) scans one (1) week apart along with serial beta-HCG levels two (2) weeks apart that are inconsistent with pregnancy and a Gynecology consult to ensure that the beta- HCG level was at a value high enough to see pregnancy with TVUS. 9. Subjects are required to agree to practice effective birth control (i.e., abstinence, intrauterine device for female subjects) during the study period. 10. Subjects must be ≥4 weeks beyond major surgical procedures such as thoracotomy, laparotomy or joint replacement, and must be ≥1.5 weeks beyond minor surgical procedures such as biopsy of subcutaneous tumors, pleuroscopy, etc., and must not have evidence of wound dehiscence, active wound infection, or comparable major residual complications of the surgery. Note: placement of pleurex catheter is not considered minor surgery for this study. 11. ANC \>1500/mm3, platelet count \>100,000/mm3 ≤14 days of study treatment 12. PT and PTT \<1.25 times the institutional upper limit of normal ≤14 days of study treatment 13. Adequate renal function documented by serum creatinine of ≤1.5 mg/dl or calculated creatinine clearance \>50 ml/min ≤14 days of study treatment 14. Adequate hepatic function as documented by serum bilirubin \<1.5 mg/dl and SGOT and SGPT ≤2.5 X upper limit of normal ≤14 days of study treatment 15. Subjects with asymptomatic brain metastases that have been treated are eligible if the following criteria are met: No history of seizures in the preceding 6 months. Definitive treatment must have been completed ≥4 weeks prior to start of study treatment. Subjects must be off steroids that were being administered because of brain metastases or related symptoms for ≥2 weeks prior to start of study treatment. Post-treatment imaging ≤2 weeks of informed consent must demonstrate stability or regression of the brain metastases. 16. Stable cardiac condition with a left ventricular ejection fraction ≥40% ≤28 days of study treatment Exclusion Criteria: 1. Subject is female who is pregnant or breast-feeding. 2. Subject received investigational therapy (i.e., agents that are not FDA-approved), including monoclonal antibodies such as bevacizumab or cetuximab, or has received radiotherapy to the skull, spine, thorax or pelvis within ≤30 days of start of study treatment. Subjects are permitted to have received palliative radiotherapy to an extremity provided ≥14 days have elapsed since completion of radiotherapy, provided the subject received ≤10 radiotherapy fractions and a dose ≤30 Gy to that site, and provided skull, spine, thorax or pelvis were not in the radiotherapy field. 3. Subject received standard chemotherapy with FDA-approved agents within ≤21 days of start of study treatment. 4. Subject received a targeted therapy within ≤14 days prior to start of study treatment. 5. Subject has active systemic viral, bacterial or fungal infection(s) requiring treatment. 6. Subject has brain metastases (except as allowed in Section 3.2.1). Neurological assessment will be used to determine brain metastases. 7. Subject has serious concurrent illness or psychological, familial, sociological, geographical, or other concomitant conditions that, in the opinion of the investigator, would not permit adequate follow-up and compliance with the study protocol. 8. Subject received prior gene therapy or cell therapy. 9. Subject has history of myocardial infarction or unstable angina ≤6 months of start of study treatment. 10. Subject is known to be HIV positive.