Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (ELAINEIII)

Sermonix Pharmaceuticals

Status and phase

Enrolling

Phase 3

Conditions

Metastatic Breast Cancer

Treatments

Drug: Lasofoxifene in combination with abemaciclib

Drug: Fulvestrant in combination with abemaciclib

Study type

Interventional

Funder types

Industry

Identifiers

NCT05696626

SMX 22-002

Details and patient eligibility

About

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.

Enrollment

500 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.
At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue.
Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy.
Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
Adequate organ function
Able to swallow tablets
Brain metastases are allowed only if the following 4 parameters hold:
1. Asymptomatic,
2. Definitively treated (e.g., radiotherapy, surgery),
3. Not requiring steroids up to 4 weeks before study treatment initiation, AND
4. Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI).
Able to understand and voluntarily sign a written informed consent before any screening procedures.

Exclusion criteria

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.
Subjects with a known hypersensitivity to fulvestrant or to any of the excipients
Radiotherapy within 30 days prior to Visit 0 (Day 1) except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1).
Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4/6i. (Screening for RB1 mutation is not required for entry.)
History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of >480 msec.
History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia.
Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure [CHF] or prolonged immobilization).
On concomitant strong CYP3A4 inhibitors.
On strong and moderate CYP3A4 inducers.
Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.
Active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics or antifungals at the time of initiating study treatment).
Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery.
Positive serum pregnancy test (only if premenopausal).
Sexually active premenopausal women and men unwilling to use double-barrier contraception.
Women who are breast feeding
History of non-compliance to medical regimens.
Unwilling or unable to comply with the protocol.
Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

500 participants in 2 patient groups

Treatment

Experimental group

Description:

Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.

Treatment:

Drug: Lasofoxifene in combination with abemaciclib

Reference Therapy

Active Comparator group

Description:

Treatment:

Drug: Fulvestrant in combination with abemaciclib