First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE₂-receptor E-type 4 (EP4), in patients with advanced cancers.

ABSTRACT:

Background

E7046 is a highly selective, small-molecule antagonist of the E-type prostanoid receptor 4 (EP4) for prostaglandin E2, an immunosuppressive mediator of the tumor immune microenvironment. This first-in-human phase 1 study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD) and recommended phase 2 dose of E7046.

Methods

This first-in-human study enrolled 30 patients with advanced tumors of cancer types associated with high levels of myeloid infiltrates. E7046 was administered orally once-daily in sequential escalating dose cohorts (125, 250, 500, and 750 mg) with ≥6 patients per cohort. Tumor assessments were performed every 6 weeks. Paired tumor biopsies and blood samples, before and on treatment, were collected for p

SUBMITTER: Hong DS 

PROVIDER: S-EPMC7304851 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature