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

• Status: Not yet recruiting
• Trial end date: 2026-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared with that of fulvestrant and abemaciclib for the treatment of 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.

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sermonix Pharmaceuticals Inc.
• Treatments: Fulvestrant

Criteria

Inclusion Criteria:

1. Pre- or postmenopausal women or men.

2. 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.

3. No evidence of progression for at least 6 months on an AI/CDK1 combination for advanced breast cancer.

4. 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.

5. Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.

6. Subjects who may have received 1 cytotoxic chemotherapy regimen for metastatic disease and/or those who received 1 cytotoxic chemotherapy regimen in either the neo-adjuvant or adjuvant setting.

7. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1

8. Adequate organ function

9. Able to swallow tablets

10. Able to understand and voluntarily sign a written informed consent before any screening procedures.

Exclusion Criteria:

1. Lymphangitic carcinomatosis involving the lung.

2. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.

3. Presence of brain metastasis.

4. Prior progression of disease on fulvestrant, or other SERD therapy.

5. 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).

6. 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.)

7. History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of >480 msec.

8. History of a PE, DVT, or any known thrombophilia.

9. On concomitant strong CYP3A4 inhibitors.

10. On strong and moderate CYP3A4 inducers.

11. Any significant co-morbidity that would impact the study or the subject's safety.

12. History of a positive human immunodeficiency virus (HIV) or hepatitis B virus (HBV) test. Screening is not required for enrollment.

13. Hepatitis C virus (HCV) at Screening who still have a viral load. Subjects previously treated and achieved HCV cure (no viral load) can be entered into the study.

14. 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, or early-stage cervical cancer.

15. Positive serum pregnancy test (only if premenopausal).