A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3)

Lilly

Status and phase: Active, not recruiting; Phase 3

Conditions: Neoplasm Metastasis; Breast Neoplasms

Treatments: Drug: Abemaciclib; Drug: Fulvestrant; Drug: Imlunestrant; Drug: Exemestane

Study type: Interventional

Funder types: Industry

Identifiers

NCT04975308

18175

J2J-OX-JZLC (Other Identifier)

2023-506786-63-00 (EU Trial (CTIS) Number)

2021-000079-35 (EudraCT Number)

Details and patient eligibility

About

The main purpose of this study is to measure how well imlunestrant works compared to standard hormone therapy, and how well imlunestrant with abemaciclib work compared to imlunestrant in participants with breast cancer that is estrogen receptor positive (ER+) and human epidermal receptor 2 negative (HER2-). Participants must have breast cancer that is advanced or has spread to another part of the body. Study participation could last up to 5 years.

Enrollment: 874 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a diagnosis of ER+, HER2- locally advanced or metastatic breast cancer

• Have disease that has demonstrated progression on or after an aromatase inhibitor alone or in combination with a cyclin-dependent kinase (CDK)4/6 inhibitor

  -- Participants are expected to have received prior treatment with a CDK4/6 inhibitor, if this treatment is approved and can be reimbursed

• Must be deemed appropriate for treatment with endocrine therapy

• If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression

• Have RECIST evaluable disease (measurable disease and/or nonmeasurable bone-only disease)

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982)

• Have adequate renal, hematologic, and hepatic organ function

• Must be able to swallow capsules/tablets

Exclusion criteria

• Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, or any investigational-ER-directed therapy (including SERDs and non-SERDs), any PI3K-, mTOR- or AKT- inhibitor
• Have visceral crisis, lymphangitic spread within the lung, or any evidence of leptomeningeal disease.
• Have symptomatic or untreated brain metastasis.
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study
• Known allergic reaction against any of the components of the study treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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874 participants in 3 patient groups

Arm A: Imlunestrant

Experimental group

Description:

Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.

Treatment:

Drug: Imlunestrant

Arm B: Investigator's Choice of Endocrine Therapy

Experimental group

Description:

Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.

Treatment:

Drug: Exemestane

Drug: Fulvestrant

Arm C: Imlunestrant + Abemaciclib

Experimental group

Description:

Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.

Treatment:

Drug: Imlunestrant

Drug: Abemaciclib