Background: 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, using serial imaging of tumor FES uptake during treatment with the SERD fulvestrant, demonstrated that significant residual FES binding uptake in tumor lesions was associated with early disease progression in patients with metastatic breast cancer (1). Methods: RAD1901-106 is Phase 1 study of RAD1901 in metastatic breast cancer patients to explore the use of FES-PET imaging as an early indicator of clinical response of RAD1901 treatment. Serial FES-PET imaging will be used to evaluate the effect of RAD1901 treatment on the availability of ER binding sites in tumor lesions. For patients demonstrating a attenuation of ER binding in tumor lesions after 14 days of RAD1901, RAD1901 treatment will continue to be administered until disease progression, unacceptable toxicity or patient’s choice and several dose levels may be explored. Key inclusion criteria include patients aged ≥ 18 years, with advanced ER positive, HER2 negative breast cancer, who have received ≤ 3 prior line of endocrine therapy in the metastatic setting. Patient enrollment started in early 2016 and is ongoing. ClinicalTrials.gov identifier: NCT02650817 (1) van Kruchten m et al, Cancer Discov. 2015:72-81 Clinical trial information: NCT02650817