Study Ttc-352-101: Phase 1 Study Of Ttc-352 In Patients With Metastatic Breast Cancer (Bc) Progressing On Endocrine Therapy.

TPS1108Background: 75% of all breast cancers (BC) are hormone receptor-positive (HR+). Despite the efficacy of endocrine therapies, HR+ BC develop resistance, and cytotoxic chemotherapy is ultimately the only option to treat these patients. TTC-352 is a selective human estrogen receptor (ER) partial agonist (ShERPA) that was developed for treatment of HR+ BC. ShERPAs mimic the effects of estradiol (E2) in hormone-independent, endocrine-resistant BC cells, but since it has only partial agonist activity in HR+ BC cells, it could have an improved side effect profile. Specifically, TTC-352 does not support the growth of HR+, hormone-dependent BC xenografts that normally require E2 for growth nor result in uterine proliferation in mouse xenograft models as does E2. PKCa is a predictive biomarker for response to TTC-352 in endocrine-resistant BC xenografts. Thus, TTC-352 could be a promising treatment option for endocrine-resistant BC. Methods: This is an open-label, accelerated dose escalation study that will ...