This early phase 1 trial will investigate the combination of low-dose interleukin-2 (IL-2) and pembrolizumab in patients with previously untreated stage IV non-small cell lung cancer (NSCLC). Preclinical data demonstrate reinvigoration of exhausted T cells into an effector-like phenotype with improved anti-tumor activity in response to this combination. This study will evaluate T cell function as well as clinical outcomes associated with this combination therapy.
Patients must have Stage IV non-small cell lung cancer (NSCLC), based on the 8th edition of the American Joint Committee on Cancer (AJCC) NSCLC Staging System. This includes adenocarcinoma and squamous cell carcinoma.
Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
No prior therapy for advanced NSCLC.
Patients with brain metastasis are eligible if they are asymptomatic or treated and stable.
Any prior chemotherapy or immunotherapy for advanced lung cancer.
Prior treatment with anti-PD-1 or anti-PD-L1 therapies or pathway-targeting agents.
Any targetable driver mutation (e.g. ALK, EGFR exon 19 del, etc).
Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
Single group
Aldesleukin
Biological/VaccineGiven SC
Pembrolizumab
Biological/VaccineGiven IV
Immune Response To Combination IL-2 and Pembrolizumab
Percentage of patients that express a greater than 1.5-fold increase in Ki-67 + PD-L1 + CD8 T cells in peripheral blood by week 3 of combination therapy. A 95% exact confidence interval will be estimated using the Clopper-Pearson method. Descriptive statistical analysis will be utilized to determine frequencies and percentages for categorical measurements.
Objective Response Rate
Will be calculated as proportion (Yes/\[Yes + No\]) along with 95% confidence intervals using the Clopper-Pearson method. Chi-square test or Fisher's exact test will be used to compare the response rate between the different groups stratified by dose level or other factors, respectively. Logistics regression model will be further employed to test the adjusted effect of dosage on the response rate after adjusting for other clinical factors and demographic factors.
Progression Free Survival (PFS)
Will be estimated alone with 95% confidence interval (CI). Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' PFS after adjusting for other factors.
Overall Survival (OS)
Will be estimated alone with 95% CI. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' OS after adjusting for other factors.
Dose-limiting Toxicities (DLTs)
Will be summarized descriptively, and percentage of DLTs will be reported. Tumor response, assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, will be summarized descriptively using frequencies and percentages. Paired assessments of mean expression will be compared using paired t-tests or Wilcoxon signed rank tests, where appropriate. Statistical significance will be assessed using the 0.05 level, and analysis will be performed using SAS 9.4.
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Emory University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
