A Phase 2 Study Of Investigational Torc1/2 Inhibitor Tak-228 With Fulvestrant In Women With Er+/Her2-Advanced Or Metastatic Breast Cancer (Mbc) That Has Progressed During Or After Aromatase Inhibitor (Ai) Therapy

TPS1118Background: Antiestrogen therapy, including AI, is standard for ER+ tumors in the adjuvant and metastatic setting; however, resistance is common. These tumors may respond to alternative second-line anti-estrogen therapies such as fulvestrant but response durations are often short. Preclinical and clinical studies suggest that simultaneous inhibition of ER and PI3K/mTOR could prevent/delay the emergence of hormone-independent cancer cells, thereby improving patient (pt) outcomes. This study will test whether fulvestrant plus TAK-228, a dual TORC1/2 inhibitor, can overcome endocrine therapy resistance in ER+ mBC. This is an open-label, randomized, phase 2 study of continuous once-daily TAK-228 (4 mg) or once-weekly TAK-228 (30 mg) plus fulvestrant (per label), vs fulvestrant alone, in pts with ER+/HER2– advanced or mBC that has progressed during/after AI therapy (EudraCT 2015-003612-20). Methods: 153 pts will be randomized 1:1:1 and stratified (presence or absence of visceral metastasis, prior hormon...