Study of Trastuzumab Deruxtecan (T-DXd) in Combination With a RAGE Inhibitor in Patients With T-DXd-Resistant HER2-Positive or HER2-Low Metastatic Breast Cancer

Inclusion Criteria: 1. Male or female ≥18 years of age at time of consent. 2. Written informed consent is required before performing any trial-specific tests or procedures. Signing of the informed consent form can occur outside the 28-day screening period. 3. Histologically confirmed HER2-positive or HER2-low or ultra low metastatic breast cancer. 4. Prior systemic progression in metastatic setting on T-DXd and have measurable disease per RECIST v1.1 Criteria. 5. ECOG performance status of 0-2 at time of consent. 6. Hematology laboratory values of: 1. Absolute neutrophil count ≥ 1500 cells/mm3 2. Platelets ≥100,000 cells/mm3 3. Hemoglobin ≥9 g/dL 4. White blood count ≥3000 cells/mm3. 7. Hepatic laboratory values of aspartate transaminase (AST) or alanine aminotransferase (ALT): 1. \<5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or 2. \<2.5 × ULN if no liver metastases are present. 8. Serum albumin \>2.8 g/dL. 9. Total bilirubin \<1.7 mg/dL × ULN. 10. Prothrombin time (PT) or international normalized ratio (INR) \<1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits. 11. Serum creatinine or serum urea \<1.5 × ULN. 12. Estimated glomerular filtration rate \>50 mL/min. 13. Urine dipstick or urinalysis with protein \<2+ or 24-hour urine protein \<1.0 g/24-h. Subjects with 1+ proteinuria must undergo a 24-hour urine collection to assess urine protein level. 14. Any CNS metastases allowed if stable. Brain metastases needing immediate local intervention allowed. Patients can still be included after local intervention like radiation or surgery if there are any other sites of systemic progressive metastases. Patients must wait for at least 2 weeks after intracranial SRS before beginning study treatment) 15. Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of study treatment. 16. Patients must be able to swallow oral capsules 17. Willing to able to comply with study procedures. Exclusion Criteria: 1. Positive pregnancy test, pregnant, or breastfeeding for all women of child-bearing potential. 2. Per treating physician's assessment, any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study. 3. Any clinically significant and/or uncontrolled pathologic cardiac-related abnormality that would compromise patient safety or the outcome of the study including, but not limited to: 1. Symptomatic valvular disease 2. Symptomatic congestive heart failure is classified by the New York Heart Association as Class III or IV 3. Unstable angina pectoris. 4. Myocardial infarction within the past 6 months from consent. 5. Active bleeding diathesis. 6. Receiving chronic treatment with corticosteroids ≥20 mg of prednisone per day (or equivalent) or other systemic immunosuppressive agents. Topical or nasal corticosteroids are allowed. 7. Uncontrolled hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV)-1 or HIV-2. 8. History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption. 9. History of malignancy or active treatment for malignancy other than breast cancer (i.e., radiation or chemotherapy, including monoclonal antibodies) within 5 years. Note: Patients with squamous or basal cell carcinomas of the skin, carcinomas in situ of the cervix or uterus, ductal breast cancer in situ, resected low-grade prostate cancer, or other malignancies that in the opinion of the investigator are considered cured may participate. 10. Receipt of live, attenuated vaccine (e.g., intranasal influenza, measles, mumps, rubella, varicella) or close contact with someone who has received a live, attenuated vaccine within the past 1 month from consent. Note: Influenza vaccine will be allowed if administered \>21 days. 11. Receipt of any investigational agent or study treatment within the past 30 days from consent for a condition other than breast cancer. 12. Receipt of any protein or antibody-based therapeutic agents (e.g., growth hormones or monoclonal antibodies) within the past 3 months from consent for a condition other than breast cancer. 13. Active infection requiring treatment (patients can be included as soon as they are off antibiotics; no wash-out period) 14. Adults unable to consent 15. Intracranial oligo progression alone (if patient is only progressing in the brain and not systemically, he/she cannot be included in the study)