First-In-Human Effects of PPT1 Inhibition Using the Oral Treatment with GNS561/Ezurpimtrostat in Patients with Primary and Secondary Liver Cancers.

ABSTRACT:

Introduction

GNS561/Ezurpimtrostat is a first-in-class, orally bioavailable, small molecule that blocks cancer cell proliferation by inhibiting late-stage autophagy and dose-dependent build-up of enlarged lysosomes by interacting with the palmitoyl-protein thioesterase 1 (PPT1).

Methods

This phase I, open-label, dose-escalation trial (3 + 3 design) explored two GNS561 dosing schedules: one single oral intake 3 times a week (Q3W) and twice daily (BID) continuous oral administration in patients with advanced hepatocellular carcinoma, cholangiocarcinoma, and pancreatic adenocarcinoma or colorectal adenocarcinomas with liver metastasis. The primary objective was to determine GNS561 recommended phase II dose (RP2D) and schedule. Secondary objectives included evaluation of the saf

SUBMITTER: Harding JJ 

PROVIDER: S-EPMC9218623 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature