Phase 2 Study of Perioperative Lenvatinib with Pembrolizumab in Patients with Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma 3215

Abstract Description Combination therapy with checkpoint inhibitors and targeted therapy represents a new horizon treatment for renal cell carcinoma (RCC). Lenvatinib is an oral multi-tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, RET, and c-Kit. Pembrolizumab is a humanized immunoglobulin G4 monoclonal antibody binding to the programmed cell death 1 (PD-1) receptor. We conducted a phase 2, single-arm trial of lenvatinib with pembrolizumab for 12 weeks in 17 patients with locally advanced biopsy-proven non-metastatic clear cell RCC before surgical resection and 13 cycles of adjuvant pembrolizumab monotherapy. Three patients (20%) experienced a partial response and 12 patients (80%) had stable disease. The median reduction of primary renal tumor size was 21% (range: 3-37%). There was no disease progression while on neoadjuvant therapy. No treatment grade 4 or 5 adverse events related to lenvatinib, or surgery occurred. These data suggest that lenvatinib with pembrolizumab treatment was clinically active and safe in the neoadjuvant setting. From these patients, blood and pre and post treatment tumor samples were collected. We will use flow cytometry to measure phenotypic changes in T-cell and myeloid cell surface markers in the collected PBMCs and tumor samples. We will measure CD4, CD8, HLADR, CD38, KI67, CD1c, CD25, CD16, CD14, CD11b, PD1, CD56, CD39, CD11c, CD20, CD45RA, CD141, TCF1, CD3, Tim3, FOXP3, IgD, CD28, CD19, CD3, and GZMB. This poster will report the details of this analysis. Funding Sources Funded by Merck Topic Categories Immune Mechanisms of Human Disease (HUM)