This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of RGT-419B administered orally as monotherapy OR in combination with Hormonal Therapy in subjects with HR+, HER2- locally advanced and unresectable (Stage III) or metastatic (Stage IV) breast cancer whose disease has progressed during prior therapy with an approved CDK4/6i plus hormonal therapy.
Male or female >/= 18 years old
ECOG Performance Status 0 to 1
Subjects must have histologically or cytologically confirmed diagnosis of ER+, HER2- ABC consistent with ASCO CAP guidelines that is locally advanced and unresectable (Stage III) or metastatic (Stage IV) BC.
Measurable AND evaluable lesions at baseline per RECIST v1.1.
Presence of visceral metastases with severe organ dysfunction as evidence by signs and symptoms, laboratory studies, lymphangitic spread and/or rapid progression of disease
Pregnant or planning to become pregnant
Prior irradiation to >25% of the bone marrow and/or inadequate bone marrow function or evidence of clinically significant end-organ damage
Major surgery, chemotherapy, targeted therapy, experimental agents, or radiation within 14-28 days prior to Cycle 1, Day 1