Pharmacokinetic-pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies.

ABSTRACT:

Background

CGM097 inhibits the p53-HDM2 interaction leading to downstream p53 activation. Preclinical in vivo studies support clinical exploration while providing preliminary evidence for dosing regimens. This first-in-human phase I study aimed at assessing the safety, MTD, PK/PD and preliminary antitumor activity of CGM097 in advanced solid tumour patients (NCT01760525).

Methods

Fifty-one patients received oral treatment with CGM097 10-400 mg 3qw (n = 31) or 300-700 mg 3qw 2 weeks on/1 week off (n = 20). Choice of dose regimen was guided by PD biomarkers, and quantitative models describing the effect of CGM097 on circulating platelet and PD kinetics.

Results

No dose-limiting toxicities were reported in any regimens. The most common treatment-related grade 3/4 AEs wer

SUBMITTER: Bauer S 

PROVIDER: S-EPMC8405607 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature