Pembrolizumab in Preventing Lung Cancer in Patients With Stage I-II Non-Small Cell Lung Cancer or High-Risk Pulmonary Nodules, the IMPRINT-Lung Study

Description

PRIMARY OBJECTIVE:

I. To determine whether immune checkpoint blockade using pembrolizumab eliminates persistent (on two computed tomography [CT] scans at least 3 months apart with no evidence of shrinkage or regression) high-risk indeterminate pulmonary nodules (IPNs) at 6 months after treatment initiation.

SECONDARY OBJECTIVES:

I. To determine whether immune checkpoint blockade using pembrolizumab decreases the incidence of lung cancers confirmed by histology (biopsy or resection).

II. To determine whether immune checkpoint blockade using pembrolizumab prolongs cancer free survival (disease free survival [DFS]) compared with observation in patients with high-risk IPNs.

III. To determine whether immune checkpoint blockade using pembrolizumab prolongs lung cancer-specific survival compared with observation in patients with high-risk IPNs.

IV. To determine whether immune checkpoint blockade using pembrolizumab prolongs overall survival (OS) compared with observation in patients with high-risk IPNs.

V. To assess the safety and tolerability of pembrolizumab in patients with high-risk IPNs.

VI. To assess quality of life patient reported outcomes in patients treated with pembrolizumab compared with patients under observation.

VII. To determine whether immune checkpoint blockade using pembrolizumab decreases the solid component of high-risk IPNs.

VIII. To assess the health-related quality of life (QoL) on subjects enrolled in the study.

EXPLORATORY OBJECTIVES:

I. To explore the radiographic (including radiomic features) evolution of high-risk IPNs with and without treatment of pembrolizumab and to assess their association with risks of risk of lung cancer as well as their association with clinical benefit/toxicities in patients treated with pembrolizumab.

II. To explore the germline deoxyribonucleic acid (DNA) profile and genomic evolution of circulating tumor DNA (ctDNA) of patients with high-risk IPNs and assess their association with risks of risk of lung cancer as well as their association with clinical benefit/toxicities in patients treated with pembrolizumab.

III. To explore the T cell receptor (TCR) repertoire evolution of patients with high-risk IPNs and assess their association with risks of risks of lung cancer as well as their association with clinical benefit/toxicities in patients treated with pembrolizumab.

IV. To explore the evolution of serum soluble factors, such as IFN-gamma and interferon inducible factors (such as CXCL9 and CXCL10), IL-12, TNFalpha, IL-10, TGF-beta, VEGF, IL-6, IL-8, IL-17, IL-18, C-reactive protein etc. and assess their association with risks of risks of lung cancer as well as their association with clinical benefit/toxicities in patients treated with pembrolizumab.

V. To explore the evolution of immunophenotyping or characterization of the immune cell subsets in the periphery, including, but not limited to, T cells, B cells, natural killer [NK] cells, or subpopulations of the aforementioned immune cell types and assess their association with risks of risks of lung cancer as well as their association with clinical benefit/toxicities in patients treated with pembrolizumab.

VI. To explore the evolution of microbiome and assess their association with risks of lung cancer as well as their association with clinical benefit/toxicities in patients treated with pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeat every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scans and collection of blood samples throughout the trial.

After conclusion of study treatment, patients are followed up at 3 and 6 months.