Primary Outcome Measure: Determine the recommended Phase 2 dose (RP2D) of elacestrant in combination with each of the other study drugs.
- Women or men aged ≥18 years (or the minimum age of consent in accordance with the local law), at the time of informed consent signature. Female patients may be either postmenopausal, premenopausal, or perimenopausal.
- Histopathologically or cytologically confirmed ER+, HER2-, breast cancer, per local laboratory.
- At least one measurable lesion as per RECIST version 1.1 or a mainly lytic bone lesion.
- 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.
- Serum albumin ≥3.0 g/dL (≥30 g/L)
- In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × 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.
- Active or newly diagnosed CNS metastases, including meningeal carcinomatosis.
- Patients with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term.
- Prior chemotherapy or elacestrant 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 known to be HIV+ are allowed as long as they have undetectable viral load at baseline.
- Documented pneumonitis/ILD prior to Cycle 1 Day 1.
- Major surgery within 28 days before starting trial therapy.
- Inability to take oral medications, refractory or chronic nausea, gastrointestinal conditions, history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impact the absorption of the 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.
- Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after trial therapy discontinuation
- 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 for anticancer antibody based treatment) or 5 half-lives, whichever is shorter,
- Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter (Refer to this Drug Interactions explanation).
- Herbal preparations/medications within 7 days.
- Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to randomization.
- Evidence of ongoing alcohol or drug abuse as assessed by the investigator.
Other inclusion/exclusion criteria are present. Please contact the study team for a complete list.