Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort.

ABSTRACT:

Objective

This phase I clinical study (NCT01415297) evaluated the safety, tolerability, maximum-tolerated dose (MTD), pharmacokinetics and pharmacodynamics of IT-139 (formerly NKP-1339) monotherapy in patients with advanced solid tumours. IT-139, sodium trans-(tetrachlorobis(1H-indazole)ruthenate(III)), is a novel small molecule that suppresses the stress induction of GRP78 in tumour cells. GRP78 is a key regulator of misfolded protein processing, and its upregulation in tumours is associated with intrinsic and drug-induced resistance.

Methods

Forty-six patients with advanced solid tumours refractory to treatment received intravenous infusions of IT-139 on days 1, 8 and 15 for every 28 days, and doses were evaluated across nine cohorts at 20, 40, 80, 160, 320, 420, 500, 625

SUBMITTER: Burris HA 

PROVIDER: S-EPMC5548977 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature