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 can mediate resistance to endocrine therapies in BC. Taselisib is a potent and selective PI3K inhibitor that displays greater selectivity for mutant PI3Kα than wild-type PI3Kα. 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. The study enriches for pts with PIK3CA-mutant tumors who will be randomized separately from pts with non-mutant tumors; a valid PIK3CA-mutation result in tumor tissue via central assessment is required prior to enrollment. The 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; > 100 patients have been enrolled onto study, and enrollment is ongoing. Clinical trial information: NCT02340221