Ph 1/1b/2 Multicenter, Open-Label, FIH Dose Esc & Dose Exp Study to Assess Safety and Tolerability of Orally Administered PMD-026 as a Single Agent and in Combination in Patients With Metastatic or Locally Advanced (Inoperable) RSK2+ Breast Cancer

Inclusion Criteria, Combination with fulvestrant (Part 3): * RSK2 positive from available archival or fresh tumor tissue (FFPE). * Histologically or cytologically diagnosed HR+, HER2- * ESR1 wild type * Diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amendable to resection or radiation with curative intent or metastatic disease not amendable to curative therapy * Must be appropriate candidates for endocrine therapy * Previously received at least 1 line of endocrine therapy for MBC or had recurrence while on adjuvant endocrine therapy for locally advanced breast cancer * Discontinued endocrine therapy at least 15 days prior to first dose of PMD-026 * At least 1 measurable target lesion as defined by RECIST v1.1 * Progression on or after treatment with a CDK4/6 inhibitor in combination with endocrine therapy inhibitor in the locally advanced or metastatic setting * Adequate hematologic, hepatic, and renal function as assessed by laboratory parameters * Toxicity related to prior therapy resolved to at least Grade 1 (alopecia excepted) or to at least Grade 2 with prior approval of the Medical Monitor Exclusion Criteria, Combination with fulvestrant (Part 3): * Prior chemotherapy * ESR1 mutations * ≤14 days from biological or investigational therapy * Presence of visceral crisis or uncontrolled visceral disease for which chemotherapy would be indicated * Central nervous system metastases, unless appropriately treated and neurologically stable * History of leptomeningeal metastases * Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy * Known hepatitis B or hepatitis C infection * Known HIV-positive with CD4+ cell counts \<350 cells/μL * Known HIV-positive with a history of an AIDS-defining opportunistic infection * History of clinically significant cardiovascular abnormalities, including QTcF interval \>460 msec (using Fridericia's formula)