Giredestrant is an investigational, oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist for hormone receptor-positive breast cancer.
It competitively binds to wild-type and mutant estrogen receptors (ER), outcompeting estradiol.
It induces an inactive receptor conformation that prompts proteasome-mediated degradation, suppressing ER-mediated cell growth.
In the Phase III evERA trial, giredestrant plus everolimus cut the relative risk of disease progression or death by 44% overall and by 62% in tumors with ESR1 mutations compared to standard endocrine therapy plus everolimus.
Early-Stage Breast Cancer: In the Phase III lidERA trial, adjuvant giredestrant lowered the risk of invasive disease recurrence or death by 30% versus standard-of-care endocrine therapy.
In combination with Everolimus leads to a significantly longer progression free survival than standard endocrine therapy-everolimus among patients with ER positive, HER2 negative advanced breast cancer who had received CDK4/6 inhibitor previously mainly in patients with ESR1-mutated tumors.
FDA Submissions: The FDA accepted new drug applications for giredestrant with priority: review as an adjuvant treatment for early-stage breast cancer and in combination with everolimus for ESR1-mutated advanced/metastatic breast cancer.