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

Prior treatment

• Prior chemotherapy
• ≤14 days from biological or investigational therapy

Other illness

• Presence of visceral crisis or uncontrolled visceral disease for which chemotherapy would be indicated
• 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 a history of an AIDS-defining opportunistic infection
• History of clinically significant cardiovascular abnormalities, including QTcF interval \>460 msec (using Fridericia's formula)

Lab values

• Known HIV-positive with CD4+ cell counts \<350 cells/μL

Other

• ESR1 mutations
• Central nervous system metastases, unless appropriately treated and neurologically stable

• 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