Study of Neoadjuvant Cemiplimab and Dupilumab in Early-Stage Non-Small Cell Lung Cancer

Inclusion Criteria:

* Histological confirmation of NSCLC is required before treatment (however, patients with a smoking history and radiographic findings suggestive of NSCLC may consent prior to biopsy to combine research and diagnostic procedures.
* Age ≥ 18 years.
* ECOG performance status 0-1
* Determined to be a surgical candidate for tumor resection by a multidisciplinary team.
* Women of childbearing potential and men must use approved contraception during the study and for 4 months post-treatment. Pregnancy or suspected pregnancy must be reported immediately.
* Adequate organ and marrow function.
* Pre-treatment biopsies are mandatory, and tumors must be T1b or larger (\>1cm) and amenable to biopsy as determined by a multidisciplinary team.
* Patients must consent to provide blood at designated study time points.
* Patients must consent to core needle biopsies (at least 3 samples, as deemed safe by the performing surgeon/radiologist) prior to treatment initiation

Exclusion Criteria:

* History of autoimmune disorders or use of immunomodulatory drugs (including dupilumab) within 2 months prior to treatment initiation.
* Active autoimmune disease requiring systemic treatment in the past year, excluding replacement therapies like thyroxine or insulin.
* Use of immunosuppressive drugs or systemic steroids within 7 days prior to treatment, except chronic steroids ≤10mg prednisone or equivalent.
* No smoking history or confirmed tissue or ctDNA evidence of actionable driver alterations (e.g. EGFR mutation, ALK, or ROS1 rearrangements)
* Prior chemotherapy or radiotherapy for another primary tumor, or prior locoregional therapy to the target lesion. Therapy for a different cancer is acceptable.
* Metastatic disease where surgery would not have curative intent.
* Uncontrolled illness, including active infections requiring antibiotics, symptomatic heart failure, unstable angina, or psychiatric/social conditions impeding study compliance.
* Pregnancy or nursing, due to potential harm to the fetus or infant.
* Progressive malignancy requiring active treatment, except for certain stable cancers treated with curative intent
* HIV infection with detectable viral load or not on a stable HAART regimen
* Active Hepatitis B or C (PCR-detectable)
* History of allogeneic hematopoietic or solid organ transplantation.
* Documented hypersensitivity to protein therapeutics.
* Any condition, therapy, or abnormality that may interfere with trial results, patient participation, or their best interest as per the investigator's judgment.