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A Phase I Study of GGTI-2418 (Geranylgeranyl Transferase I Inhibitor) in Patients with Advanced Solid Tumors

A Phase I Study of GGTI-2418 (Geranylgeranyl Transferase I Inhibitor) in Patients with Advanced... Background Geranylgeranyltransferase I (GGTase I) catalyzes geranylgeranylation, a modification required for the function of many oncogenic RAS-related proteins. GGTI-2418 is a peptidomimetic small molecule inhibitor of GGTase I. Objective The aim of this study was to establish the maximum tolerated dose of GGTI-2418 in patients with advanced solid tumors. Patients and Methods This was a phase I, open-label, dose-escalation study conducted in two US centers (University of Pennsylvania and Indiana University) in adults with treatment-refractory advanced solid tumors. An accelerated dose-esca- lation schema was used across eight dose levels, from 120 to 2060 mg/m , administered on days 1–5 of each 21-day cycle. Results Fourteen patients were enrolled in the dose-escalation cohort. No dose-limiting toxicities were observed, and 2060 mg/m was determined to be the maximum tolerated dose. The only potential drug-related grade 3 or 4 toxicities were elevated bilirubin and alkaline phosphatase in a single patient with concurrent malignant biliary obstruction. No objec- tive responses were observed. Four of thirteen evaluable patients had stable disease for up to 6.7 months. The study was terminated prior to dose expansion based on a sponsor decision. Pharmacokinetic analysis demonstrated a mean terminal half-life of 1.1 h. Conclusions GGTI2418 was safe and tolerable at all tested http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Targeted Oncology Springer Journals

A Phase I Study of GGTI-2418 (Geranylgeranyl Transferase I Inhibitor) in Patients with Advanced Solid Tumors

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References (13)

Publisher
Springer Journals
Copyright
Copyright © 2019 by Springer Nature Switzerland AG
Subject
Medicine & Public Health; Oncology; Biomedicine, general
ISSN
1776-2596
eISSN
1776-260X
DOI
10.1007/s11523-019-00661-5
Publisher site
See Article on Publisher Site

Abstract

Background Geranylgeranyltransferase I (GGTase I) catalyzes geranylgeranylation, a modification required for the function of many oncogenic RAS-related proteins. GGTI-2418 is a peptidomimetic small molecule inhibitor of GGTase I. Objective The aim of this study was to establish the maximum tolerated dose of GGTI-2418 in patients with advanced solid tumors. Patients and Methods This was a phase I, open-label, dose-escalation study conducted in two US centers (University of Pennsylvania and Indiana University) in adults with treatment-refractory advanced solid tumors. An accelerated dose-esca- lation schema was used across eight dose levels, from 120 to 2060 mg/m , administered on days 1–5 of each 21-day cycle. Results Fourteen patients were enrolled in the dose-escalation cohort. No dose-limiting toxicities were observed, and 2060 mg/m was determined to be the maximum tolerated dose. The only potential drug-related grade 3 or 4 toxicities were elevated bilirubin and alkaline phosphatase in a single patient with concurrent malignant biliary obstruction. No objec- tive responses were observed. Four of thirteen evaluable patients had stable disease for up to 6.7 months. The study was terminated prior to dose expansion based on a sponsor decision. Pharmacokinetic analysis demonstrated a mean terminal half-life of 1.1 h. Conclusions GGTI2418 was safe and tolerable at all tested

Journal

Targeted Oncology – Springer Journals

Published: Aug 1, 2019

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