This is a multi-site, global, open-label study that includes a phase 1b evaluation of elacestrant in combination with abemaciclib in women and men with brain metastases from estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER-2) negative breast cancer. Phase 1b was designed to select the recommended phase 2 dose (RP2D) and is followed by an ongoing phase 2 evaluation of elacestrant in combination with abemaciclib in participants with active brain metastases from ER-positive, HER-2 negative breast cancer.
Participant has the signed informed consent form before any study-related activities according to local guidelines.
Women or men aged ≥18 years, at the time of informed consent signature.
Age ≥60 years
Age <60 years and amenorrhea for 12 or more months without an alternative cause) and follicle stimulating hormone and estradiol in postmenopausal ranges per local reference ranges
Immediate CNS-specific treatment is likely to be required, per the treating physician's assessment.
Participant has imminent organ failure and/or visceral crisis.
Participant has leptomeningeal metastases, defined as having positive cerebrospinal fluid (CSF) cytology or unequivocal radiologic and clinical evidence of leptomeningeal involvement. Note: Discrete dural metastases are permitted.
Breast cancer treatment-naïve participants (that is, not having received any systemic therapy) in the advanced/metastatic setting.
Sequential
Elacestrant
Drug300 mg, 400 mg
Abemaciclib
Drug100 mg, 150 mg
Phase 1b: RP2D
Based on the observed number of dose-limiting toxicities (DLTs) during the first cycle. Dose-limiting toxicity is based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs will be evaluated during the first cycle (28 days) of treatment in up to 3 cohorts during Phase 1b. A DLT will be defined as any of the toxicities listed in the protocol that are not clearly due to breast cancer or extraneous causes.
Phase 2: Objective Response Rate (ORR) Per Overall Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)
Defined as the proportion of participants with a best overall response (BOR) of either a confirmed complete response (CR) or partial response (PR) per blinded independent central review (BICR).
Phase 1b and 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Phase 1b and 2: Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau)
Phase 1b and 2: Maximum Observed Plasma Concentration (Cmax)
Phase 1b and 2: Time to Reach Cmax (Tmax)
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