Cemiplimab and Fianlimab Before Surgery for the Treatment of Stage IB-IIIB Non-Small Cell Lung Cancer

PRIMARY OBJECTIVES: I. To assess efficacy of neoadjuvant cemiplimab and fianlimab in patients with resectable/early-stage NSCLC with PD-L1 1-49%, as measured by rate of major pathologic response (MPR) (defined as ≤ 10% viable tumor cells in resected tumor and lymph nodes). II. To assess efficacy of neoadjuvant cemiplimab and fianlimab in patients with resectable/early-stage NSCLC with PD-L1 ≥ 50%, as measured by rate of major pathologic response (MPR). SECONDARY OBJECTIVES: I. Assess the following endpoints (overall and by PD-L1 subsets): event-free survival (EFS), overall survival (OS), disease-free survival (DFS), response rate, pathological complete response rate (pCR), surgical feasibility, and adverse events. OTHER GOALS (done overall and by PD-L1 subsets): I. Assess the following in an exploratory fashion: residual viable tumor cells using various cutpoints, whole exome sequencing (WES), gene copy number analysis, circulating tumor deoxyribonucleic acid (DNA) (ctDNA) analysis, tumor microenvironment (TME) analysis, microbiome analyses, temporal biomarker changes. II. Assess LAG-3 expression on immune-cells by immunohistochemistry (IHC) (17B4) and MHC-II and FGL1 expression by on tumor cells and correlate with clinical data like MPR rate, EFS, and OS. III. Determine any correlation between the above biomarkers with clinical data of interest like the MPR rate, EFS, and OS. IV. Determine ctDNA testing as a marker for minimal residual disease (MRD) and molecular recurrence. V. Determine radiomic and pathomic markers of response to therapy. OUTLINE: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle and fianlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) during screening, tissue sample collection on study, and blood sample collection, computed tomography (CT), and positron emission tomography (PET)/CT throughout the study. Patients may undergo SOC surgery post-treatment. After completion of study treatment, patients are followed up at 90 days, then every 3 months post-surgery for the first 2 years, then every 6 months for up to 5 years.