FDA Grants Lasofoxifene Fast Track Designation for ER+/ESR1-Mutant Metastatic Breast Cancer

The FDA has granted a fast track designation to lasofoxifene for use as a treatment of female patients with estrogen receptor–positive, HER2-negative metastatic breast cancer who harbor ESR1 mutations.

The FDA has granted a fast track designation to lasofoxifene for use as a treatment of female patients with estrogen receptor (ER)—positive, HER2-negative metastatic breast cancer who harbor ESR1 mutations.1

The investigational agent is being evaluated in comparison with fulvestrant (Faslodex) in the phase II ELAINE trial, which is enrolling up to 100 postmenopausal patients with acquired ESR1-mutant locally advanced or metastatic ER-positive, HER2-negative breast cancer.

“We are very encouraged to receive Fast Track designation, a recognition of lasofoxifene’s potential promise as a precision medicine for women with ER-positive metastatic breast cancer,” Anthony H. Wild, PhD, chairman of Sermonix, said in a press release.

Lasofoxifene is a nonsteroidal selective estrogen receptor modulator under investigation as a potential precision medicine therapy for women with breast cancer who harbor ESR1 mutations, as the agent has demonstrated activity against mutations of the ER. ESR1 mutations are commonly found in the metastatic setting in breast cancers, for the most part among women who have progressed on prior endocrine treatment, leading to an unmet need.

The open-label, randomized, multicenter phase II ELAINE study NCT03781063 will enroll patients of this subgroup with an acquired ESR1 mutation, as detected by a cell-free circulating-tumor DNA liquid biopsy test, who have progressed on an aromatase inhibitor in combination with a CDK4/6 inhibitor. Eligible patients must have received 1 prior chemotherapy regimen in the neoadjuvant or adjuvant setting and have an ECOG performance score of 0 or 1.

The primary endpoint of the study is progression-free survival; secondary endpoints include clinical benefit rate, objective response rate, duration of response, time to response, overall survival, and safety. An exploratory analysis will also explore the presence of select mutations, including NF1 and KRAS, from tumor-free DNA.

Preclinical findings for lasofoxifene will be presented at the 2019 ASCO Annual Meeting.2 According to the abstract, lasofoxifene demonstrated greater efficacy than fulvestrant at inhibiting metastasis in xenograph models. In addition, in a study of lasofoxifene or fulvestrant in combination with palbociclib (Ibrance) in mice, the combination of lasofoxifene and palbociclib demonstrated greater reduction of primary tumor growth. Results showed that lasofoxifene can disrupt the active conformation of the ER-alpha Y537S ligand-binding domain.

Moreover, Sermonix is looking to potential breakthrough and priority review designations for a future new drug application for the agent as a result of the fast track designation.

“Lasofoxifene’s Fast Track designation highlights the significant unmet medical needs of women who have ER-positive/HER2-negative breast cancer with an ESR1 mutation,” David Portman, MD, CEO of Sermonix, stated in the press release. “Fast Track will allow us to more quickly complete our development program and, if successful, make lasofoxifene available to patients sooner.”


  1. Sermonix Receives FDA Fast Track Designation for Investigational Drug Lasofoxifene [news release]. Columbus, OH: Sermonix Pharmaceuticals LLC; May 28, 2019. https://bit.ly/2HH9Ofm?rel=0. Accessed May 28, 2019.
  2. Laine M, Fanning SW, Greene M, et al. Lasofoxifene as a potential treatment for ER+ metastatic breast cancer. J Clin Oncol. 2019;37(suppl; abstr 1056).