Asciminib in HER2+ Breast Cancer Brain Metastases

Inclusion Criteria: * Age ≥18 years at the time of consent * Patients with HER2+ metastatic breast cancer with at least one progressive or new brain metastasis measuring \>5mm; prior local therapy to other intracranial lesions allowed * At least 1 prior standard of care therapy for metastatic disease * Must have previously received T-DXd and Tucatinib. If a patient has not received T-DXd or Tucatinib as part of standard early line therapy due to allergies or intolerability, the requirement of prior T-DXd and Tucatinib treatment is waived. * Participants must have adequate treatment washout period when applicable before enrollment, defined as: * \>4 weeks from any major surgery * \>1 week from any cranial radiation treatment * For cytotoxic containing agents, 5 half-lives or at least 21 days (whichever is shorter) * For weekly chemotherapy regimens, \>2 weeks from chemotherapy; for every 3 weekly regimens, \>3 weeks from chemotherapy. At least 2 weeks from other systemic or targeted or investigational therapies (other than endocrine therapy) for breast cancer. No washout is required for endocrine therapy (e.g. aromatase inhibitors, tamoxifen, fulvestrant) but patients should discontinue prior to start of protocol therapy. * Patients on ovarian suppression are allowed (but not required) to continue ovarian suppression at the discretion of their treating provider. * Adequate organ function and bone marrow reserve as determined by the investigator * Adequate hepatic and renal function and hematologic parameters: * Absolute neutrophil count (ANC) ≥ 1.0 × 109/L * Platelets ≥ 100 × 109/L * Hemoglobin ≥ 9 g/dL * Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN) * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present) * Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault (CG) equation * Left ventricular ejection fraction (LVEF) ≥ 50%. * Females of childbearing potential must have a negative pregnancy test (serum or urine) at screening. If a pregnancy test using either method is positive or cannot be confirmed as negative, a second testing using the other method will be required for confirmation. * Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use highly effective contraception * Can enroll with intracranial disease only; extracranial disease can be absent or non-measurable * Focal leptomeningeal disease allowed at investigator discretion * Performance status by Eastern Cooperative Oncology Group (ECOG) 0-2 (appendix 1) * Written informed consent and HIPAA authorization for release of personal health information prior to enrollment. NOTE: HIPAA authorization may be included in the informed consent or obtained separately Exclusion Criteria: * No evidence of hemorrhage or impending herniation or need for immediate local therapy to intracranial disease or escalating dosing of steroids * No grade 2 or greater peripheral neuropathy * Diffuse and symptomatic leptomeningeal carcinomatosis * Prolonged Qtc (QTcF\>450), CHF or uncontrolled HTN * Clinically significant cardiopulmonary disease. * Acute or chronic pancreatitis within 6 months prior to first day of study treatment * Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including: * tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice), * hepatitis B (known positive HBV surface antigen (HBsAg) result) , * hepatitis C (note: hepatitis C testing at screening will only be performed on those at high risk or with known history), or * human immunodeficiency virus (positive HIV 1/2 antibodies) (note: HIV testing at screening will only be performed on those at high risk or with known history) * NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed if they are stable and have been on treatment for ≥ 4 weeks prior to first dose of study drug(s). Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy. Testing not required. * Unable for any reason to undergo MRI of the brain. * Use of a strong cytochrome P450 (CYP)3A4 inhibitor within 5 half-lives of study treatment. .. Unable to avoid certain CYP3A4 or CYP2C9 substrates which cannot be co-administered with study treatment given altered substrate concentrations. * Central nervous system exclusion - Based on screening brain MRI, patients must not have any of the following: * Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent) * Diffuse leptomeningeal disease or positive CSF cytology; however, discreet dural-based metastases are allowed * Poorly controlled seizures. Defined as seizures that continue to occur despite optimal anticonvulsant medications based on investigator discretion. * Active infection requiring intravenous systemic therapy. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). * Patients with a prior or concurrent malignancy within last 5 years whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial. * Treatment with any investigational drug within 30 days prior to enrollment (Day 1 of study drug).