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

Inclusion 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 6inhibitor (CDK4/6i) therapy combined with HT in the MBC setting (up to 1additional line of CDK4/6i is permitted in the post-surgical adjuvant setting);

• Subjects must have received therapy for ≥3 months in the MBC setting, orfor ≥6 months in the adjuvant setting, prior to progression

• Progression after ≤3 lines of prior HT therapy (regardless of whether it is HTalone or in combination with other therapies)

• Prior HT combination agents, including SERD, SERM or AI, must havereceived 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 consentdocument

Exclusion Criteria:

1. Presence of visceral metastases with severe organ dysfunction as evidence by signsand symptoms, laboratory studies, lymphangitic spread and/or rapid progression ofdisease

2. Pregnant or planning to become pregnant

3. Prior irradiation to >25% of the bone marrow and/or inadequate bone marrow functionor evidence of clinically significant end-organ damage

4. Major surgery, chemotherapy, targeted therapy, experimental agents, or radiationwithin 14-28 days prior to Cycle 1, Day 1

5. Active, serious medical condition that is not well controlled with locally approvedmedications allowed by the protocol

6. History of allergic reactions attributed to compounds of similar chemical orbiologic composition to the drugs used in the study