Giredestrant (GDC-9545)

Agent Description

Giredestrant is a potent, orally bioavailable, nonsteroidal oral selective estrogen receptor degrader (SERD) agent that antagonizes the effects of estrogens via competitive binding to the ligand-binding-domain (LBD) of both wild-type and mutant ER with nanomolar potency.

Mechanism of Action

Giredestrant induces an inactive conformation to the ER LBD, as measured by displacement of co-activator peptides. In addition to its direct antagonist properties, the mechanism of action of giredestrant includes reducing levels of ER protein through proteasome-mediated degradation.

Classification

Selective estrogen receptor degrader (SERD)

Molecular Targets

ER-targeting therapy

Monograph

Giredestrant is a novel, oral SERD that has demonstrated preliminary evidence of clinical activity in metastatic ER+ breast cancer, including ESR1 mutant tumors alone or in combination. It is being studied in breast cancer, rare ovarian cancer and endometrial cancers.

Studies of Interest

Trials combining Giredestrant with mechanistically rational agents in various solid tumors and trials evaluating the safety and preliminary efficacy of giredestrant in combination with other anti-cancer agents.

Information collaborator would like included in investigator proposals

Sponsor-investigator must indicate appropriate facilities/personnel, experience treating patients in desired research population and that they have an adequate sample size they can enroll into study, and a proven track record for conducting and publishing research. Formulary LOI proposal needs to describe if they have ongoing studies at their institution that would compete with the research population of interest during the expected patient accrual window.