Abstract OT2-01-21: Phase 2 study of investigational TORC1/2 inhibitor TAK-228 with fulvestrant in women with ER-positive/HER2-negative advanced or metastatic breast cancer that has progressed during or after aromatase inhibitor therapy

This study will test whether fulvestrant plus TAK-228, a dual TORC1/2 inhibitor, can overcome endocrine therapy resistance in ER-positive breast cancer. This is an open-label, randomized, 3-arm, phase 2 study of continuous once-daily TAK-228 (oral, 4 mg) or once-weekly TAK-228 (oral, 30 mg) plus fulvestrant (500 mg intramuscularly on d1 and d15 of cycle 1 [loading regimen] then d1 of each subsequent 28-d cycle), compared with fulvestrant alone, in pts with advanced or metastatic ER-positive/HER2-negative breast cancer that has progressed during/after AI therapy. Pts will be randomized 1:1:1 to the 3 arms and stratified at randomization via presence or absence of visceral metastasis, prior hormonal therapy sensitivity, and prior exposure to CDK 4/6 inhibitors. Pts will receive study drug(s) until progressive disease (PD), unacceptable toxicity, or consent withdrawal. Postmenopausal women ≥18 yrs old with local histological confirmation of ER-positive/HER2-negative metastatic or advanced breast cancer; with measureable disease; ECOG status 0–1; PD during/after prior AI therapy (defined as progression ≤12 mos after discontinuing adjuvant therapy or ≤1 mo after discontinuation in the metastatic setting) and adequate organ function are eligible. Exclusion criteria include prior therapy with mTOR inhibitors, PI3K inhibitors, dual PI3K-mTOR inhibitors, AKT inhibitors, or fulvestrant; prior treatment with>1 line of chemotherapy for metastatic breast cancer; experienced recurr...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Ongoing Clinical Trials Source Type: research