Multicenter phase 1b study of gedatolisib in combination with palbociclib and endocrine therapy for HR-positive, HER2-negative advanced breast cancer

The PI3K-mTOR pathway is frequently dysregulated in breast cancer. A multicenter phase 1b study in the United States evaluated the combination of gedatolisib (pan-PI3K-mTOR inhibitor) with palbociclib (CDK4/6 inhibitor) and endocrine therapy (letrozole or fulvestrant) for HR-positive, HER2-negative advanced breast cancer (aBC). Results of four expansion cohorts of the study have now been published: treatment-naïve in the advanced setting, progression on 1-2 lines of endocrine therapy but CDK4/6 inhibitor-naïve, and one or more previous lines of therapy, including a CDK4/6 inhibitor. In all four expansion cohorts the combination of gedatolisib with palbociclib and endocrine therapy showed a promising objective response rate compared with the published results for standard-of care therapies, and had an acceptable safety profile.