A phase 3 study of alpelisib (ALP) plus fulvestrant (FUL) in men and postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC progressing on or after aromatase inhibitor (AI) therapy: SOLAR-1.

Abstract

TPS1111 Background: Patients (pts) with HR+ breast cancer (BC) often havedysregulatedphosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, which further leads to resistance to endocrine therapy (ET). In a phase 1 study, alpelisib (BYL719), a PI3Kα-specific inhibitor in combination with fulvestrant (FUL) has demonstrated antitumor activity in pts with estrogen receptor-positive, HER2– advanced BC (ABC) with PIK3CA-altered tumors. SOLAR-1 (NCT02437318) aims to assess the efficacy of ALP + FUL in PIK3CA-mutant and non-mutant tumors in HR+, HER2– ABC setting. Methods: SOLAR-1 is a phase 3, randomized, double-blind study conducted in men and postmenopausal women with HR+, HER2– ABC. Pts are randomly (1:1) allocated to oral alpelisib/placebo (300 mg qd) and intramuscular FUL (500 mg) until disease progression or treatment (tx) discontinuation. Stratification factors are presence of liver and/or lung metastases and prior use of CDK4/6 inhibitors. The eligibility criteria for the targeted BC patient population are shown in the Table. The primary endpoint is progression-free survival (PFS; RECIST v1.1; local assessment), while overall survival (OS) is a key secondary endpoint in the PIK3CA-mutant cohort. Other secondary endpoints are PFS and OS in the PIK3CA non-mutant cohort, the association between PFS and baseline PIK3CAstatus in ctDNA, overall response rate, clinical benefit rate, and safety. Recruitment of the planned 560 pts is currently ongoing. Clinical trial information: NCT02437318. [Table: see text]