Breast cancer is the most studied malignancy in the world. It is the most common cancer among women and affects one out of every eight women in the U.S. It remains the second leading cause of cancer death in women. At least 70% of all breast cancer expresses estrogen receptor alpha (ERa), making it a prime target for the treatment of breast cancer. Despite effective endocrine therapies, many patients eventually relapse and become resistant to standard of care treatments. These endocrine resistant tumors often continue to depend on ERa for growth and survival, as evidenced by their sensitivity to the selective estrogen receptor degrader (SERD), fulvestrant. However, fulvestrant may be limited by its pharmaceutical and pharmacokinetics properties and intramuscular route of administration to achieve sufficient target occupancy for maximal efficacy. Consequently, SERDs with superior drug properties were sought after, allowing consistent and rapid achievement of therapeutic exposure. GDC-0927 is an oral SERD currently in Phase 1 clinical trial, which was discovered through a prospective lead optimization on ERa degradation. Structure of GDC-0927 will be disclosed along with preclinical characterization of potency, pharmacokinetics, and <i>in vivo</i> efficacy in wildtype and ER mutant models, as well as early clinical data.

GDC-0927, a selective estrogen receptor degrader and full antagonist for ER+ breast cancer

255th National Meeting (2018)

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