Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies and HER2 Negative Breast Cancer

Inclusion Criteria: * Age ≥ 18 * A) Advanced or metastatic solid tumor with lack of PTEN expression as determined by immunohistochemistry. Lack of PTEN expression is defined as the absence of staining in the tumor (\<5%), with strong positive staining of adjacent normal endometrium or stromal cells, using the monoclonal DAKO antibody 6H2.1.9 OR * B) Advanced or metastatic solid tumor with a deleterious somatic mutation in PTEN as determined by tissue or ctDNA testing in a CLIA laboratory and classified as deleterious in the ClinVar or COSMIC databases OR * C) Advanced or metastatic HER2 negative breast cancer. Patients must have received ≤ 3 prior cytotoxic chemotherapies for metastatic disease (immunotherapy does not count as a line of therapy), and up to 2 prior antibody drug conjugate regimens (eg, sacituzumab govitecan, trastuzumab deruxtecan). Patients with ER-positive breast cancer (ER\>10%) are eligible if they have had progressive disease after at least 1 prior CKD4/6 inhibitor. Patients must have received alpelisib or capivasertib if eligible for either therapy or must be intolerant to or have refused such therapy. °Patients with known PTEN altered breast cancer may participate regardless of lines of prior therapy if they meet criteria A or B. * Measurable disease only required for dose expansion in non-prostate ca patients * Patients with prostate cancer without measurable disease must have evaluable disease as assessed by serum PSA. * Patients must have progres…