Study of IRX4204 With Erlotinib in Previously Treated Advanced NSCLC

Inclusion Criteria: * Patients must have histologically or cytologically confirmed stage IV non-small cell lung cancer, or recurrent non-small cell lung cancer which is not amenable to curative intent therapy. * Documented disease progression on at least two prior lines of chemotherapy for advanced NSCLC. Progression within 6 months of adjuvant chemotherapy or definitive chemoradiation will count as one line of therapy. * Age ≥18 years. * ECOG performance status ≤2. * Ability to take pills by mouth. * Patients must have normal organ and marrow function as defined below: * Leukocytes ≥3,000/mcL * Absolute neutrophil count ≥1,500/mcL * Platelets ≥100,000/mcL * Hemoglobin ≥8.5 g/dL * Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) ≤2.5 × ULN or ≤5 x ULN if metastases to the liver * Creatinine clearance ≥40 mL/min * Patients with asymptomatic brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids. Maximum daily dose of steroids should be prednisone 20 mg or equivalent. Radiation therapy for brain metastases must be completed at least 14 days prior to treatment on protocol. * Women of child-bearing potential and men must agree to use highly effective contraception (if using hormonal birth control must add a second barrier method; abstinence) prior to study entry, for the duration of study participation as well as for at least 1 month after the last dose of IRX4204. Men treated or enrolled on this protocol must also agree to use highly effective contraception prior to the study, for the duration of study participation and 3 months after completion of IRX4204 administration. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study. * Activating EGFR mutations detected in the tumor. * Prior treatment with an EGFR tyrosine kinase inhibitor. * Prior treatment with IRX4204 or another retinoid or rexinoid administered for the purpose of cancer treatment. Prior topical retinoid use is allowed. * History of allergic reactions attributed to IRX4204 or erlotinib or to compounds of similar chemical or biologic composition. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and nursing women. * Patients with a history of another active malignancy within the past two years, with the exception of non-melanoma cutaneous malignancy, cervical carcinoma in situ, or ductal carcinoma in situ which has been successfully treated with curative intent therapy. * Any gastrointestinal disorder expected to limit absorption of IRX4204 or erlotinib. * Patients with a history of active thyroid disease. However, patients with a history of hypothyroidism maintained in euthyroid state by supplementation with thyroid hormone, or a thyroid hormone containing preparation may be enrolled. * Patients taking coumarin-derived anticoagulants.