Trotabresib in Combination With Vinorelbine and Radiation Therapy for the Treatment of HER2+ Breast Cancer With Central Nervous System or Leptomeningeal Metastasis

Inclusion Criteria: * Patients must have histologically or cytologically confirmed diagnosis of HER2+ breast cancer. Patients may be immunohistochemistry (IHC) 3+ and/or fluorescence in situ hybridization (FISH) positive for HER2. IHC 2+ HER2 patients are eligible with reflex FISH-positive testing with the ratio ≥ 2.0. Alternatively, circulating tumor DNA testing positive for HER2 mutation is accepted for eligibility * Patients must have newly diagnosed or progressive brain and/or leptomeningeal metastases, and a change in management and of treatment regimen is indicated. There is no limit on the number and types of prior systemic or intrathecal therapies * Subjects must have an estimated life expectancy ≥ 3 months * At registration, patients must have an interval of at least 2 weeks after the end of prior cytotoxic chemotherapy or immunotherapy or previous RT, one week from prior targeted small molecule drug treatment, interval of ≥ 4 weeks from prior bevacizumab or nitrosourea. At treatment start of trotabresib, there must be an interval of ≥ 4 weeks since last cytotoxic chemotherapy (6 weeks for prior nitrosourea) or immunotherapy * Note: Anti-HER2 directed treatment is allowed to continue, however, should be switched to trastuzumab before initiation of trotabresib. No washout period is required * Patients must be age ≥ 18 years on the day of signing consent * Patients must exhibit Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Leukocytes (WBC) ≥ 3,000/m…