SMX 22-002 - ELAINE 3 (JCP139)

An Interventional, Open-Label, Randomized, Multicenter Phase 3 Study of PF-07220060 Plus Fulvestrant Compared To Investigator`s Choice of Therapy in Participants Over 18 Years of Age with Hormone Receptor-Positive, HER2-Negative Advanced/Metastatic Breast

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Population: ER+/HER2- mBC or locally advanced, with ESR1 mutation

Line of therapy: 2L

Intervention: Lasofoxifene and Abemaciclib vs. Fulvestrant and Abemaciclib

Key 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. Histological or cytological confirmation of ER+/HER2 - disease

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

5. 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.

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

7. 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.

8. ECOG performance score of 0 or 1

9. Brain metastases are allowed only if the following 4 parameters hold: Asymptomatic, definitively treated (e.g., radiotherapy, surgery), not requiring steroids up to 4 weeks before study treatment initiation, AND Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI).

   
   

Key Exclusion Criteria

1. Lymphangitic carcinomatosis involving the lung.

2. History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.

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

4. Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (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 pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia.

9. 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).

10. On concomitant strong CYP3A4 inhibitors.

11. On strong and moderate CYP3A4 inducers.

12. Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.

13. Active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics or antifungals at the time of initiating study treatment).

14. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).

Sponsor: Sermonix

CRP Contact:  wagdy.rezk@ladydavis.ca

514-340-8222 ext. 25728

CRP PI: Dr. P. Fallah

Status: Open to accrual