• RSK2 positive from available archival or fresh tumor tissue (FFPE).

• Histologically or cytologically diagnosed HR+, HER2-

• 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