A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population

This trial is a multicenter, open-label, non-comparative, phase II, biomarker-driven adjuvant treatment study involving the periodic collection and analysis of blood samples from patients with HR-positive/HER2-negative early-stage BC at higher risk of relapse, who have undergone surgery within the previous five years, with no evidence of locoregional, contralateral, or distant disease.

The study design is composed by an initial pre-screening phase, a molecular follow-up phase (ctDNA surveillance phase), and an interventional therapeutic phase (treatment phase).

After informed consent is obtained, a total of 976 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel (tumor signature).

At the event of ctDNA positivity, patients will be screened to enter the treatment phase of the study. Upon confirmed eligibility, a total of 40 patients will be allocated in one of the following trial's arms adopting a sequential recruitment strategy:

Arm A: Control Arm (N=10) Arm B: Experimental Arm with giredestrant (N=10) Arm C: Experimental Arm with giredestrant + abemaciclib (N=10) Arm D: Experimental Arm with giredestrant + inavolisib (N=10)

If the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome, new cohorts may be added to the study.