A Randomized, Open-label, Parallel-group Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in Early ER+/HER2- Breast Cancer

What this Trial Is About

Researchers are evaluating and comparing the immune modulation effects of three FDA-approved CDK4/6 inhibitors—palbociclib, ribociclib, and abemaciclib—combined with letrozole as neoadjuvant treatment for early estrogen-receptor positive (ER+)/HER2-negative breast cancer. While all three inhibitors have shown progression-free survival benefits in advanced breast cancer, differences in overall survival might be influenced by their varying effects on the tumor microenvironment and immune system. This Phase 2 randomized study aims to provide a head-to-head comparison of these effects in the same trial. Participants will receive one of three treatment combinations: palbociclib with letrozole, ribociclib with letrozole, or abemaciclib with letrozole. These CDK4/6 inhibitors are given alongside endocrine therapy before surgery over a 12-week period. Tissue, blood, and stool samples will be collected before treatment, two weeks after starting treatment, and after 12 weeks at surgery to analyze immune-related changes through RNA sequencing of breast tumors. During the study, researchers will monitor participants for immune response changes and adverse events. The primary outcome is the change in immune-related gene expression after treatment, assessed through RNA sequencing over an average follow-up of three years. Safety will be assessed over four months. Participants’ organ function and performance status will be evaluated before and during treatment to ensure safety and compliance with study procedures.

A Randomized Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in ER+/HER2- EBC