A Phase 1b/2 Study Assessing the Safety and Efficacy of Evexomostat (SDX-7320) in Combination with a PI3K Pathway Inhibitor plus Fulvestrant in Postmenopausal Women with Advanced Breast Cancer and PI3K Pathway Alterations Who Have Progressed on or Following Endocrine Therapy plus a CDK4/6 Inhibitor
Objective
Primary Objective: To establish the safety and appropriate dose of evexomostat (SDX-7320) dosed in combination with either alpelisib or capivasertib and fulvestrant (i.e., triplet therapy) in post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer with alterations in the PI3K pathway, including PIK3CA mutation, PTEN loss, or AKT1 mutation following treatment on endocrine therapy plus a CDK 4/6 inhibitor.
Secondary Objectives: Safety: To measure the severity, number and proportion of patients with any grade hyperglycemia events. To measure the number and type of agents needed to control alpelisib- or capivasertib-induced hyperglycemia. To measure change in glycated hemoglobin (HbA1c) from baseline (Cycle 1, Day 1 [C1D1]) to C5D15 and at End-of-Treatment (EOT).
Tumor Burden, Pharmacokinetics (PK), and Quality of Life (QoL): To determine the effect of treatment with evexomostat in combination with either alpelisib or capivasertib and fulvestrant on the objective respo nse rate (ORR) in post-menopausal women with metastatic HR+, HER2- breast cancer with PI3K pathway alterations (as detailed above).To assess the clinical benefit rate (CBR) of patients on the triplet therapy. To assess the number of patients alive without disease progression at 6 months of triplet therapy. To characterize exposure of evexomostat and its metabolite(s) when administered in combination with fulvestrant alone and with either alpelisib or capivasertib plus fulvestrant. Assessment of QoL scale on the European Organization for Research and Treatment of Cancer
