Biomarker results and preclinical rationale for combination lenvatinib and pembrolizumab in advanced endometrial carcinoma.
2018
5597Background:
Lenvatinib(
LEN) is a multikinase inhibitor of VEGFR 1−3, FGFR 1−4, and other targets;
pembrolizumab(PEM) is an anti–PD-1 antibody. We report biomarker analyses from a phase 1b/2 trial in advanced endometrial cancer (EC) and preclinical rationale for the activity of combination
LEN+ PEM. Methods: In an exploratory analysis, 41 candidate serum biomarkers for
LENand PEM were assessed using immunoassay panels in 38 patients with EC receiving
LEN+ PEM at baseline, cycle 1 day 15 (C1D15), and C2D1. Data cutoff: May 31, 2017.
Tumor-associated macrophages(TAM) were assessed in mouse
syngeneictumor models by flow cytometry and immunohistochemistry. RNAseq transcriptomes of tumors from mice treated with
LEN, anti–PD-1, or
LEN+ anti–PD-1 were subjected to weighted gene coexpression network analysis for pathway enrichment analyses. Results: At C1D15 and C2D1 of
LEN+ PEM, significant changes were seen in the levels of 16 and 18 of 41 biomarkers, respectively, including increased levels of inte...
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