Hutchison China MediTech (Chi-Med) has commenced a Phase I/II clinical trial of HMPL-453 in China for the treatment of solid tumours in patients carrying fibroblast growth factor receptor (FGFR) genetic alteration.
HMPL-453 is a highly selective and potent small-molecule inhibitor of fibroblast growth factor receptors (FGFR) one, two and three.
Designed to complement an ongoing Phase I trial in Australia, the multi-centre, single-arm, open-label, two-part Phase I/II trial will investigate the safety, tolerability, preliminary efficacy and pharmacokinetics (PK) of HMPL-453 as a monotherapy.
The initial dose-escalation part of the trial will include locally advanced or metastatic solid tumour patients for whom, irrespective of their genetic status, standard therapy does not exist or was ineffective or intolerable
The first part will establish the maximum tolerated dose (MTD) and recommended dose for Phase II.
The second dose-expansion part will assess the safety, tolerability, preliminary anti-tumour efficacy and PK at the recommended Phase II dose.
Patients with FGFR dysregulated tumours and other solid tumours such as advanced bladder cancer and advanced cholangiocarcinoma will be included in the second part.
The primary endpoint of the dose-expansion part is objective response rate (ORR), while secondary endpoints include safety, duration of response (DoR), progression-free survival (PFS), disease control rate (DCR) and overall survival (OS).
According to the data from pre-clinical studies, HMPL-453 indicated superior potency, better kinase selectivity and a favourable safety profile, when compared to other drugs belonging to the same class.