The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation.
The main question the study aims to answer is:
• To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.
Pre- or postmenopausal women or men.
Locally advanced and/or metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease.
Histological or cytological confirmation of ER+/HER2 - disease
No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer.
Lymphangitic carcinomatosis involving the lung.
History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.
Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy.
Parallel
Lasofoxifene in combination with abemaciclib
Drug5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day
Fulvestrant in combination with abemaciclib
DrugFulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day
Progression free survival (PFS)
PFS is defined as the time from the date of randomization \[Visit 0 (Day 1)\] to the earliest date of first documented progression per RECIST 1.1 as determined by BICR or death due to any cause.
Objective response rate (ORR)
ORR is defined as the percentage of subjects with measurable disease at baseline whose best overall response is either a confirmed CR or a confirmed PR according to RECIST 1.1.
Overall survival (OS)
Overall survival is defined as time from the date of Visit 0 (Day 1) to death due to any cause.
Clinical benefit rate (CBR)
CBR is defined as the percentage of subjects with best overall response of confirmed CR, confirmed PR, or stable disease (SD) with a duration of 24 weeks or longer according to RECIST 1.1. As used in this calculation, stable disease is defined as stable disease in those subjects with measurable disease plus nonPR/non progressive disease (PD) in subjects with non-measurable disease.
Duration of response (DoR) in subjects with an objective response
DoR is from the date of first documented confirmed response (CR or PR) to the date of first documented progression of disease or death due to any cause, whichever is earlier.
