H3 Biomedicine, a member of Eisai’s Oncology business group, has started dosing patients in a Phase I clinical trial of H3B-6545 as a monotherapy to treat breast cancer.
H3B-6545 is an orally bioavailable, potent and selective small molecule antagonist of wild-type and mutant oestrogen receptor (ERα).
The drug candidate belongs to a new ERα antagonist class known as selective oestrogen receptor covalent antagonists (SERCA) that inactivate oestrogen receptor.
The open-label, multi-centre, dose-escalation and expansion Phase I trial will assess the safety, pharmacokinetics, pharmacodynamics and clinical activity of once-daily H3B-6545 on a 28-day cycle in ER-positive, Her2-negative breast cancer patients.
H3 Biomedicine chief scientific officer Peter Smith said: “The initiation of this study represents a significant milestone for our company, as it marks the third programme from our portfolio to enter the clinic in the past 12 months.
“Through this study, we anticipate creating significant clinical data to guide our future development plans for this first-in-class covalent antagonist of the oestrogen receptor.”
The initial dose-escalation portion of the trial will include administration of increasing doses of oral H3B-6545 to establish the maximum tolerated dose (MTD) and / or the recommended Phase II dose according to the safety and tolerability observed.
The dose expansion portion will further investigate the recommended Phase II dose’s safety, tolerability and clinical activity.
During preclinical studies, H3B-6545 demonstrated improved activity and inhibition of cell line growth and patient-derived xenograft models of wild-type and mutant ERα compared to standard-of-care treatments.