Neoadjuvant Dupilumab and Cemiplimab in Patients With Early-stage Resectable NSCLC

Eligibility Criteria

• * Patients with history of autoimmune disorder or any patient who has used an immunomodulatory drug, such as dupilumab, within 8 weeks of starting treatment.
• * Patients without any smoking history, or any patient for whom we already have tissue or ctDNA evidence of an activating EGFR mutation or an ALK or ROS1 rearrangement.
• * Patients who have had chemotherapy or radiotherapy within 4 months prior to entering the study for a different primary tumor, nor can they have received locoregional therapy (e.g. radiation) for the target lesion that will be biopsied and subsequently resected. Previous therapy for a different cancer (a different primary) is acceptable.
• * Patients may not be receiving any other investigational agents.
• * Patients with metastatic disease, for whom the intent of surgery would not be curative.
• * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements, as determined the treating investigator.
• * Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• * Use of another immunomodulatory drug, including dupilumab, that may confound interpretation of clinical and biospecimen analysis, within 8 weeks of enrollment.
• * Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the administration of trial treatment. Patients on chronic steroids equivalent to ≤ 10mg prednisone will not be excluded.
• * Has active autoimmune disease that has required systemic treatment in the past 1 year (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 acceptable.
• * Has a known additional malignancy that is progressing and requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical or anal cancer, prostate cancer on stable dose of hormonal therapy without rising PSA, and breast cancer whom have been treated with curative intent, who may be on hormonal therapy.
• * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• * HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen.
• * Has known active Hepatitis B (e.g., HBV detected by PCR (\>200 IU/ml) or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• * Patients whom have recently started (\>14d from C1D1) antiviral therapy may go on to the trial.
• * History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
• * Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps)
• * Principle investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient.
• * Any evidence of current ILD or pneumonitis or a prior history of ILD or pneumonitis requiring oral or IV glucocorticoids.