Biopharmaceutical company Hutchison China MediTech (Chi-Med) has begun the first-in-human (FIH) Phase I clinical trial of HMPL-453 to treat patients with advanced or metastatic solid malignancies in Australia.
HMPL-453 is a new, highly selective and potent small-molecule inhibitor developed to target fibroblast growth factor receptor (FGFR) 1/2/3 with an IC50 in the low nanomolar range.
A sub-family of receptor tyrosine kinases, the activation of FGFRs signalling pathways is reported to be the primary requirement for multiple biological processes such as angiogenesis, tissue growth and repair.
The disruption of this signalling is found to cause tumour growth, enhance angiogenesis and resistance to anti-tumour therapies.
The open-label, dose-escalation Phase I trial will evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of HMPL-453 in patients, who have failed or are unable to tolerate standard therapies or for whom no standard therapies exist.
The FIH study is designed to be conducted in two preliminary phases, including a dose-escalation (stage 1) and a dose-expansion stage (stage 2).
The preclinical studies of HMPL-453 showed anti-tumour activity with comparitively better potency and kinase selectivity that was consistent with the target inhibition in tumour models with abnormal FGFR activation.
The drug was found to have good pharmacokinetic properties such as rapid absorption after oral dosing, good bioavailability, as well as moderate tissue distribution and clearance in all pre-clinical animal species.
Hutchison MediPharma, the innovation platform of the firm discovers and develops new therapeutics for oncology and autoimmune diseases, while its commercial platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
