Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer

Inclusion Criteria:

• Adult female or male participants.

• ER+, HER2- locally advanced or metastatic breast cancer that is not amenable tocurative therapy.

• Evaluable disease (measurable disease per RECIST 1.1 or bone-only disease).

• De novo advanced breast cancer or with disease recurrence occurring after 12 monthsof completing adjuvant endocrine therapy (with or without CDK4/6 inhibitors)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Adequate hematologic, hepatic, and renal functions.

• Female participants can be pre-, peri- or postmenopausal.

• Male and pre- or peri-menopausal female participants must be willing to take a GnRH (or LHRH) agonist.

Exclusion Criteria:

• Disease recurrence during adjuvant endocrine therapy

• Currently receiving or previously received systemic anti-cancer therapy for ER+,HER2- advanced breast cancer.

• Previously received treatment with fulvestrant, elacestrant or an investigationalendocrine therapy in any setting.

• History of allergic reactions to study treatment.

• Any contraindications to letrozole and ribociclib.

• Symptomatic central nervous system metastases, carcinomatous meningitis,leptomeningeal disease, or a spinal cord compression that require immediatetreatment.