Abstract OT1-03-14: SANDPIPER: Phase III study of the PI3-kinase inhibitor taselisib (GDC-0032) plus fulvestrant in patients with estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer enriched for patients with PIK3CA-mutant tumors
Authors: Baselga J , Cortés J , De Laurentiis M , Diéras V , Harbeck N , Hsu J , Jin H , Schimmoller F , Wilson TR , Im Y-H , Jacot W , Krop IE , Verma S 
Published: May 2016

Abstract
Background: PIK3CA mutations are one of the most frequent genomic alterations in breast cancer (BC), being present in ∼40% of estrogen receptor (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 PI3-kinase (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 patients with PIK3CA-mutant BC treated with taselisib either as a single agent or in combination with fulvestrant.
Trial design: SANDPIPER is a double-blind, placebo-controlled, randomized, phase III study, designed to evaluate efficacy and safety of taselisib plus fulvestrant in patients with ER-positive, HER2-negative locally advanced or metastatic BC. Patients will be randomized 2:1 to receive either taselisib (4 mg daily) 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 patients with PIK3CA-mutant tumors who will be randomized separately from patients with non-mutant tumors.
Eligibility: Postmenopausal women with ER-positive, HER2-negative, locally advanced or metastatic BC are eligible if they have disease recurrence or progression during or after aromatase inhibitor treatment. A valid PIK3CA-mutation result via central assessment is required prior to enrollment.
Aims: The primary efficacy endpoint is investigator-assessed progression-free survival (PFS) in patients with PIK3CA-mutant tumors. Other endpoints include overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), duration of objective response, safety, pharmacokinetics, and patient-reported outcomes. Efficacy in patients without PIK3CA-mutant tumors will be an exploratory endpoint.
Statistical methods: The primary efficacy analysis population will include all randomized patients with PIK3CA-mutant tumors. Patients will be grouped according to treatment arm assigned at randomization. Median PFS and OS will be estimated using Kaplan-Meier methodology in each treatment arm. Cox proportional-hazards models will be used to estimate the hazard ratio with 95% confidence intervals (CIs). ORR, CBR, and their 95% CIs will be estimated by treatment arms. Duration of objective response will be estimated by treatment arms using the Kaplan-Meier methodology. Quality of life will be analyzed and summarized by treatment arms. Safety will be analyzed for all treated patients according to actual treatment received.
Accrual: Target enrollment is 600 pts from ∼165 sites and ∼23 countries. The study is open for enrollment and 11 patients have been enrolled as of May 31, 2015. Clinicaltrials.gov ID: NCT02340221.
Contact information: For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only).
Citation Format: Baselga J, Cortés J, De Laurentiis M, Diéras V, Harbeck N, Hsu J, Jin H, Schimmoller F, Wilson TR, Im Y-H, Jacot W, Krop IE, Verma S. SANDPIPER: Phase III study of the PI3-kinase inhibitor taselisib (GDC-0032) plus fulvestrant in patients with estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer enriched for patients with PIK3CA-mutant tumors. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-14.