This phase II trial tests how well a fixed dose combination (FDC) of cemiplimab and fianlimab before surgery (neoadjuvant) works in treating patients with stage IB-IIIB non-small cell lung cancer (NSCLC). The current standard of care (SOC) for NSCLC is to give chemotherapy and immunotherapy before going to surgery to have the cancer removed (neoadjuvant therapy). Immunotherapy with monoclonal antibodies, such as cemiplimab and fianlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving a FDC of cemiplimab and fianlimab before surgery may kill more tumor cells in treating patients with stage IB-IIIB NSCLC.
PRIMARY OBJECTIVES: I. To assess efficacy of neoadjuvant cemiplimab and fianlimab in patients with resectable/early-stage NSCLC with programmed death-ligand 1 (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 major histocompatibility complex class II (MHC-II) and fibrinogen-like protein 1 (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. 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 on study and follow-up. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Undergo tissue and blood sample collection
Given IV
Given IV
Undergo MRI
Undergo SOC surgery
Mayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGMajor pathologic response (MPR) rate (Group A)
Will be defined as ≤ 10% viable tumor cells in resected tumor and lymph nodes. Will be conducted using two parallel Simon two-stage trial designs. Will be evaluated within the PD-L1 1-49% group.
Time frame: Up to 2 years
MPR rate (Group B)
Will be defined as ≤ 10% viable tumor cells in resected tumor and lymph nodes. Will be conducted using two parallel Simon two-stage trial designs. Will be evaluated within the PD-L1 ≥ 50% group.
Time frame: Up to 2 years
Event-free survival (EFS)
Defined as the time from study entry to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause (whichever occurs first).
Time frame: Up to 5 years
Overall survival (OS)
Defined as the time from study entry to death from any cause.
Time frame: Up to 5 years
Disease-free survival (DFS)
Defined as the time from surgery to the first of either disease recurrence or death from any cause.
Time frame: Up to 5 years
Overall response rate (ORR)
Will be calculated based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. A tumor response is defined to be either a complete response or partial response noted as the objective status during neoadjuvant treatment.
Time frame: Up to 5 years
Pathologic complete response (pCR) rate
Defined as 0% residual viable tumor (complete absence of tumor) in the resected lung and lymph node tissue. Will be reported as pCR rate, defined as the proportion of patients who achieve pCR after neoadjuvant treatment at the time of resection
Time frame: Up to 5 years
Surgical feasibility - to surgery
Will be assessed by the number of participants who make it to surgery
Time frame: Up to 5 years
Surgical feasibility - complete surgery
Will be assessed by the number of participants who complete surgery
Time frame: Up to 5 years
Incidence of adverse events
The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Frequency and percentage of Grade 3+ adverse events will be summarized.
Time frame: Up to 90 days after last study treatment, up to 2 years
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