A randomized, double-blind, Phase III Study of AZD9833 plus CDK4/6 inhibitor in patients with metastatic breast cancer with detectable ESR1 mutation

Prior treatment

• Previous treatment with AZD9833, investigational SERDs or fulvestrant.
• Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor and/or AI treatment.

Other illness

• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
• Any evidence of severe or uncontrolled systemic diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
• Patient with known or family history of severe heart disease

Other

• Advanced, symptomatic, visceral spread, that are at risk of lifethreatening complications in the short term
• Currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

• Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent.
• Documentation of histologically confirmed diagnosis of estrogen receptor positive (ER+) /HER2- breast cancer based on local laboratory results.
• Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor ± LHRH as the initial endocrine based treatment for advanced disease
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• ESR1m detected by central testing of ctDNA
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Adequate organ and marrow function