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

Eligibility Criteria

• 1. Male or female \>/= 18 years old
• 2. ECOG Performance Status 0 to 1
• 3. 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.
• 4. Measurable AND evaluable lesions at baseline per RECIST v1.1.
• 5. 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
• 6. Adequate organ function
• 7. Ability to understand and the willingness to sign a written informed consent document
• 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
• 2. Pregnant or planning to become pregnant
• 3. Prior irradiation to \>25% of the bone marrow and/or inadequate bone marrow function or evidence of clinically significant end-organ damage
• 4. Major surgery, chemotherapy, targeted therapy, experimental agents, or radiation within 14-28 days prior to Cycle 1, Day 1
• 5. Active, serious medical condition that is not well controlled with locally approved medications allowed by the protocol
• 6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study