Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Exclusion criteria

• . Lymphangitic carcinomatosis involving the lung.
• . Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
• . Radiotherapy within 30 days prior to entry into the study except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to entry into the study. Subjects must have recovered from radiotherapy toxicities prior to entry into the study.
• . Subjects with known inactivating RB1 mutations or deletions (Screening for RB1 mutation is not required for entry).
• . History of long QTC syndrome or a QTC of \> 480 msec.
• . History of a pulmonary embolus (PE) or deep vein thrombosis (DVT) within the last 6 months or any known thrombophilia. Subjects stable on anti-coagulants for maintenance are eligible as long as the DVT and/or PE occurred \> 6 months prior to enrollment and there is no evidence for active thrombosis. The use of low-dose ASA is permitted.
• . Subjects on concomitant strong CYP3A4 inhibitors such as clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir.
• . Subjects on strong and moderate CYP3A4 inducers such as amprenavir, barbiturates, carbamazepine, clotrimazole, dexamethasone, efavirenz, ethosuximide, griseofulvin, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, chronic prednisone treatment, primidone, rifabutin, rifampin, rifapentine, ritonavir, topiramate.