ELACESTRANT in Women and Men With CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer Study

Inclusion Criteria:

Patient has signed the informed consent before all study specific activities are conducted.

Women or men aged ≥18 years (or the minimum age of consent as per local law), at the time of informed consent signature. Female patients may be either postmenopausal or premenopausal or perimenopausal.

Premenopausal or perimenopausal women and men must be concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 4 weeks before the start of trial therapy and is planning to continue LHRH during the study.
For perimenopausal women to be considered of non-childbearing potential, FSH levels must be >40 mIU/mL.
Documentation of histopathologically or cytologically confirmed ER+, HER2-breast cancer, per local laboratory, as per the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al, 2020, Wolff et al, 2018). Note: In the context of this trial, ER status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry.
Patient has received at least one (and up to two) prior hormonal therapy in the advanced/metastatic setting.
At least one measurable lesion as per RECIST version 1.1 or a mainly lytic bone lesion. Note: Patients with stable brain or subdural metastases are allowed if the patient has completed local therapy and was on a stable or decreasing dose of corticosteroids at baseline for management of brain metastasis for at least 4 weeks before starting treatment in this study. The dose must be ≤2.0 mg/day of dexamethasone or equivalent. Any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
ECOG performance status of 0 or 1.

Patient has adequate bone marrow and organ function, as defined by the following laboratory values:

Absolute neutrophil count (ANC) ≥1.5 × 109/L
Platelets ≥100 × 109/L
Hemoglobin ≥9.0 g/dL
Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE grade ≤1
Cockcroft-Gault based creatinine clearance ≥50 mL/min. Note: Creatinine clearance (male) = ([140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72)
Serum albumin ≥3.0 g/dL (≥30 g/L)
In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper limit of normal (ULN). If the patient has liver metastases, ALT and AST ≤5 × ULN
Total serum bilirubin <1.5 × ULN except for patients with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN.

Exclusion Criteria:

Active or newly diagnosed central nervous system (CNS) metastases, including meningeal carcinomatosis.
Patients with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial) and liver involvement of >50%.
Prior chemotherapy, elacestrant, or CDK4/6i in the advanced/metastatic setting.
Patient has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, with the exception of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative therapy.
Uncontrolled significant active infections.
Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection must have undetectable viral load during screening.
Patients known to be HIV+ are allowed as long as they have undetectable viral load at baseline.
Major surgery or radiotherapy within 28 days before starting trial therapy.
Inability to take oral medication, refractory or chronic nausea, gastrointestinal condition (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that may impact the absorption of study drug.
Known intolerance to elacestrant or any of its excipients.
Females of childbearing potential who within 28 days before starting trial therapy, did not use a highly effective method of contraception.
Females of childbearing potential who do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after trial therapy discontinuation. Note: Please refer to "Recommendations related to contraception and pregnancy testing in clinical trials" for additional details.
Men who do not agree to abstain from donating sperm, or to use a highly effective method of contraception, during the course of the treatment period and for 120 days thereafter.

Patient is currently receiving or received any of the following medications prior to first dose of trial therapy:

Investigational anti-cancer therapy within 14 days (28 days in case of anticancer antibody-based treatments) or 5 half-lives, whichever is shorter.
Fulvestrant treatment (last injection) <42 days before first dose of study drug.
Any other endocrine therapy <14 days before first dose of study drug.
Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter.
Herbal preparations/medications within 7 days. These include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng.
Evidence of ongoing alcohol or drug abuse as assessed by the investigator.