NEW YORK – Sermonix Pharmaceuticals is starting a Phase III trial of endocrine therapy lasofoxifene for patients with locally advanced or metastatic ER+/HER2-breast cancer with an estrogen receptor 1 (ESR1) mutation, the company said on Thursday.
Sermonix has partnered with Guardant Health for the trial and will use the Guardant360 CDx liquid biopsy assay, a blood-based sequencing test that detects mutations from circulating tumor DNA, to determine eligibility by screening patients for ESR1 variants.
The trial, dubbed the ELAINE-3 study, will compare lasofoxifene against fulvestrant, an estrogen receptor antagonist, both in combination with Eli Lilly's CDK4/6 inhibitor Verzenio (abemaciclib). The trial will enroll pre- and post-menopausal patients who have progressed on CDK4/6 inhibitors palbociclib or ribociclib in combination with an aromatase inhibitor and up to one line of chemotherapy. Lasofoxifene, an ESR1 antagonist that works particularly well in the presence of ESR1 mutations, could provide a treatment option for patients with such mutations who have acquired endocrine resistance, according to the company.
Patients will be randomized to either lasofoxifene or fulvestrant while also receiving 150 milligrams of Verzenio twice a day. The primary endpoint for the study is progression-free survival, with secondary endpoints including overall response rate, overall survival, clinical benefit rate, duration of response, time to disease recurrence, and time to chemotherapy.
Sermonix expects to dose the first patient for the trial in the first half of this year and plans to enroll 400 patients in total.
The trial builds on previous positive results from the ELAINE-1 and ELAINE-2 trials.
"We look forward to further studying lasofoxifene in a large, rigorously designed Phase III study, which will include the use of the Guardant360 CDx test to identify patients who have an ESR1 mutation upon progression after first line therapy," said Paul Plourde, Sermonix's VP for clinical oncology development, in a statement.