ERADICATE: Hormone and Targeted Therapy for HR+/HER2-Low Advanced Breast Cancer

About the Study

This study is looking at the safety and effectiveness of elacestrant, a hormone therapy that blocks estrogen receptors to help prevent cancer cells from growing, in combination with trastuzumab deruxtecan (T-DXd), a targeted treatment that combines an antibody directed at HER2 with a chemotherapy drug. The study is for people with hormone receptor-positive (HR+), HER2-low or HER2-ultralow breast cancer that has spread to other parts of the body (metastatic) or is locally advanced and cannot be removed with surgery. Participants must have cancer that has progressed despite treatment with a CDK4/6 inhibitor and hormone therapy.

What the study Involves

This is a Phase Ib/II clinical trial.

• Phase Ib: Researchers will evaluate the safety and side effects of the drug combination and determine the recommended dose for the next phase.

• Phase II: Researchers will further evaluate how well the combination works and its safety at the recommended dose.

Participants will receive elacestrant in combination with trastuzumab deruxtecan. The study involves medical assessments and tests to monitor participants' health, side effects, and response to treatment. The research team will provide details about the treatment schedule and required tests.

• People aged 18 or older.
• People with hormone receptor-positive, HER2-low or HER2-ultralow breast cancer that is metastatic or locally advanced and cannot be removed with surgery.
• People who have previously received a CDK4/6 inhibitor and hormone therapy for metastatic breast cancer.
• People who have received up to one prior line of chemotherapy or an antibody-drug conjugate for metastatic disease.
• People whose ESR1 mutation status is known from tumor testing or a blood-based tumor DNA test.
• People whose cancer can be measured on imaging tests.
• People who are able to take medication by mouth and meet the study's other health and safety requirements.

• Have previously received a topoisomerase inhibitor antibody-drug conjugate.
• Have received certain oral estrogen receptor-targeting medications for metastatic breast cancer, such as elacestrant-like drugs in the SERD, SERM, PROTAC, or CERAN categories. Prior treatment with fulvestrant is allowed.
• Have brain metastases that are causing symptoms or require immediate treatment. Some people with stable or symptom-free brain metastases may be eligible.
• Have had a serious allergic reaction to drugs similar to either study drug.
• Have received another investigational drug or device within two weeks before starting this study.
• Have certain lung conditions, including a history of noninfectious pneumonitis that required steroid treatment or current interstitial lung disease.
• Are pregnant or breastfeeding.
• Have certain uncontrolled medical conditions or another cancer history that does not meet the study's eligibility requirements.