Phase 1/1b/2 Study of Oral PMD-026 in Patients With Metastatic Breast Cancer

Inclusion Criteria

• 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)