An Open, Randomized, Multicenter Study Evaluating the Activity of Lasofoxifene Relative to Fulvestrant for the Treatment of Postmenopausal Women with Locally Advanced or Metastatic ER+/HER2- Breast Cancer with an ESR1 Mutation
This is an open label, randomized, multicenter study evaluating the activity of lasofoxifene relative to fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer with an acquired ESR1 mutation and who have disease progression on an aromatase inhibitor (AI) in combination with a cyclin dependent kinase (CDK) 4/6 inhibitor. The primary objective is to evaluate the progression free survival (PFS) of 5 mg lasofoxifene relative to fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an ESR1 mutation.---- The secondary objectives are to evaluate:-- 1.Clinical benefit rate (CBR) and Objective Response Rate (ORR)-- 2.Duration of response-- 3.Time to response-- 4.Overall Survival (OS)-- 5.Pharmacokinetics of lasofoxifene-- 6.Quality of life (QoL)-- 7.Safety of lasofoxifene-- 8.Response to various ESR1 mutation subtypes-- 9.The presence of the following mutations from tumor free DNA will be documented and part of an exploratory analysis:-- a.) erbb2 extracellular domain mutation 5310;-- b.) erbb2 kinase domain mutations V777, L755, and Exon 20 insertion;-- 3.all NF1 mutations that are truncating, frame shifting and nonsense or homozygous deletions; and-- 4.KRAS.