FIH Study of RGT-419B Alone and With Endocrine Therapy in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer

Inclusion criteria

• 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.
• Eligible subjects must meet all of the following criteria:

• Progression after receiving 1 line of prior cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) therapy combined with HT in the MBC setting (up to 1 additional line of CDK4/6i is permitted in the post-surgical adjuvant setting);

• Subjects must have received therapy for ≥3 months in the MBC setting, or for ≥6 months in the adjuvant setting, prior to progression
• Progression after ≤3 lines of prior HT therapy (regardless of whether it is HT alone or in combination with other therapies)

• Prior HT combination agents, including SERD, SERM or AI, must have received formal approval by regulatory agency.
• ≤ 1 prior line of chemotherapy in the metastatic setting
• Adequate organ function
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• 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
• Active, serious medical condition that is not well controlled with locally approved medications allowed by the protocol
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study