Background: PIK3CA mutations are one of the most frequent genomic alterations in BC, being present in ~40% of ER-positive, HER2-negative breast tumors. PIK3CA mutations promote growth and proliferation of tumors and mediate resistance to endocrine therapies in BC. Taselisib is a potent and selective PI3K inhibitor of the alpha, gamma, and delta isoforms, with 30-fold less inhibition of the PI3K beta isoform relative to the alpha isoform. Taselisib has enhanced activity against PIK3CA-mutant BC cell lines, and clinical data include confirmed partial responses in pts with PIK3CA-mutant BC treated with taselisib either as a single agent or in combination with fulvestrant. SANDPIPER, a double-blind, placebo-controlled, randomized, phase III study, is designed to evaluate efficacy and safety of taselisib plus fulvestrant in postmenopausal pts with ER-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic BC. Methods: Pts with disease recurrence or progression during or after aromatase inhibitor treatment will be randomized 2:1 to receive either taselisib (4 mg qd) or placebo in combination with fulvestrant (500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each subsequent 28-day cycle). Randomization will be stratified by visceral disease, endocrine sensitivity, and geographical region. Pts with PIK3CA-mutant tumors (n = 480) will be randomized separately from pts with non-mutant tumors (n = 120); a valid PIK3CA-mutation result via central assessment is required prior to enrollment. Primary efficacy endpoint is investigator-assessed progression-free survival in pts with PIK3CA-mutant tumors. Other endpoints include overall survival, objective response rate, clinical benefit rate, duration of objective response, safety, pharmacokinetics, and patient-reported outcomes. Target enrollment is 600 pts from ~165 sites and ~23 countries. The study is active as of February 2015. NCT02340221. Clinical trial information: NCT02340221