First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma.

ABSTRACT:

Purpose

TGFβ signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGFβ signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a first-in-human dose (FHD) study in patients with cancer.

Experimental design

Sixty-five patients (58 with glioma) with measurable and progressive malignancies were enrolled. Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28-day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). Safety was as

SUBMITTER: Rodon J 

PROVIDER: S-EPMC4337847 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature