Safety and Effectiveness of Evexomostat Combined With a PI3K or AKT Inhibitor Plus Fulvestrant for Adults With HR, HER2- Metastatic Breast Cancer Having PI3K Pathway Changes

What this Trial Is About

Researchers are evaluating a combination treatment for men and post-menopausal women with hormone receptor positive HR, HER2-negative advanced or metastatic breast cancer that has specific alterations in the PI3K pathway, such as mutations in the PIK3CA gene, PTEN loss, or AKT1 mutation. This Phase 1b2, open-label pilot study aims to determine the safety of evexomostat combined with either alpelisib or capivasertib plus fulvestrant, measure the severity and number of hyperglycemic events, and assess the anti-tumor effects of these triplet therapies. Participants will first receive evexomostat plus fulvestrant for 14 days before adding either alpelisib or capivasertib, depending on the oncologists choice, forming the triplet therapy. Treatment cycles last 28 days, and doses of evexomostat may be adjusted based on safety data. Patients may continue the triplet therapy for up to seven cycles, or longer if clinical benefit is observed, with ongoing safety and efficacy monitoring. During the study, patients will undergo tumor assessments and monitoring of hyperglycemic events, glucose control, insulin resistance, and various biomarkers related to tumor and metabolic activity. Safety data, adverse events, and quality of life will be evaluated up to 42 to 48 months. Participants must attend scheduled visits and comply with fasting requirements on designated days. The study allows continuation of therapy until disease progression, unacceptable toxicity, or withdrawal.

Evexomostat Plus PI3K or AKT Inhibitor and Fulvestrant in Patients With a PI3K Alteration and HR+/Her2- Breast Cancer