Abstract 922: Preclinical anticancer activity of LSZ102, a novel oral selective estrogen receptor degrader targeting wild-type and mutant ER

A Phase I Study of LSZ102, an Oral Selective Estrogen Receptor Degrader, with or without Ribociclib or Alpelisib, in Patients with Estrogen Receptor–Positive Breast Cancer

“…Fulvestrant survival benefit is dose dependent ( 16, 17 ), but poor oral bioavailability mandates administration by monthly intramuscular injection, limiting clinical dosing to a maximum of 500 mg. Of note, data from the plasmaMATCH study, a multiple parallel-cohort trial of circulating tumor DNA (ctDNA)-directed therapy, failed to meet prespecified efficacy criteria despite extended-dose fulvestrant (500 mg every 2 weeks) in patients with ESR1 mutations ( 18 ). Orally available SERDs may achieve more complete ER degradation than fulvestrant ( 19 ), potentially conferring greater clinical activity. LSZ102 is an investigational oral SERD that shows single-agent activity against ESR1 -mutant models and synergistic activity with ribociclib and alpelisib in preclinical models of ER-positive breast cancer ( 19 ).…”

“…Orally available SERDs may achieve more complete ER degradation than fulvestrant ( 19 ), potentially conferring greater clinical activity. LSZ102 is an investigational oral SERD that shows single-agent activity against ESR1 -mutant models and synergistic activity with ribociclib and alpelisib in preclinical models of ER-positive breast cancer ( 19 ). We report data from a phase I, first-in-human trial of LSZ102, with or without ribociclib or alpelisib, in adults with ER-positive breast cancer.…”