A Phase 1 study of RAD1901, an oral selective estrogen receptor degrader, in ER positive, HER2 negative, advanced breast cancer patients.

Abstract

TPS627Background: RAD1901 is a novel, orally available selective estrogen receptor degrader (SERD) that binds to both mutant and wild type forms of the ER leading to ER degradation and inhibition of cellular proliferation. RAD1901 demonstrated greater growth inhibition of human breast cancer xenograft models compared to fulvestrant. In addition, RAD1901 inhibited the growth of patient-derived xenograft (PDx) models harboring ESR1 mutations. RAD1901 was evaluated in a phase 1 dose escalation study (200 mg to 1000 mg of oral RAD1901 daily) in healthy postmenopausal female volunteers (N = 52). They tolerated RAD1901 well and a dose-proportional exposure was observed based on pharmacokinetic analyses. ER occupation was assessed using 18F-fluoroestradiol positron emission tomography (FES-PET) imaging which showed that after 6 days of RAD1901 treatment the mean decrease of FES uptake ER in the uterus was 83% for the 200 mg (n = 3) and 92% at the 500 mg (n = 4) dose levels. A previously published FES-PET study, ...