Pembrolizumab With or Without Chemotherapy Before Surgery in Treating Patients With Stage I-IIIA Non-Small Cell Lung Cancer

PRIMARY OBJECTIVES: I. To determine the impact of neoadjuvant pembrolizumab-based combination therapy on the composition, phenotype, and function of tumor-infiltrating immune cells (TIICs) in patients with early stage non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To determine the safety and tolerability of neoadjuvant pembrolizumab alone and in combination with chemotherapy as measured by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0. II. To determine the clinical efficacy of neoadjuvant pembrolizumab alone and in combination with chemotherapy. EXPLORATORY OBJECTIVES: I. To explore the relationship between changes in TIICs and clinical efficacy in patients with early stage NSCLC treated with neoadjuvant pembrolizumab-based combination therapy. II. To characterize changes in the frequency and number of circulating immune cells induced by neoadjuvant pembrolizumab-based combination therapy in patients with early stage NSCLC. III. To determine the impact of neoadjuvant pembrolizumab-based combination therapy on the composition and phenotype of the tumor microenvironment (including tumor and stromal cells) in patients with NSCLC. III. To determine the change in T cell repertoire within the tumor and blood induced by neoadjuvant pembrolizumab-based combination therapy in patients with early stage NSCLC. IV. To explore molecular profiles to identify potentially predictive biomarkers for patients with early stage NSCLC treated with immunotherapy. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 4 weeks following study treatment. COHORT B: Patients receive pembrolizumab IV over 30 minutes and chemotherapy (cisplatin/pemetrexed) IV on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 4 weeks following study treatment. After completion of study treatment, patients are followed up every 3 months for up to 2 years.