NCT07214532

Signatera-Guided CDK4/6 Inhibitor Therapy in Breast Cancer

SIgnatera-Guided Initiation of Adjuvant CDK4/6 Inhibitor in Intermediate Risk HR+ HER2- Breast Cancer

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 725 (estimated)
• Sponsor: Natera, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of ctDNA-guided initiation of CDK4/6 inhibitor therapy using the Signatera™ Designed on Genome test (referred to as "Signatera Genome") in participants with intermediate-risk HR+/HER2- early-stage breast cancer. Based on ctDNA test results, participants will either start CDK4/6 inhibitor therapy in addition to hormone therapy or continue hormone therapy with ongoing ctDNA surveillance. This study will compare outcomes to historical controls from the NataLEE trial to determine whether ctDNA-guided timing maintains efficacy while reducing unnecessary treatment. Participants will be followed for up to 9 years with regular blood draws, hormone therapy, imaging as needed, and quality-of-life assessments.

Detailed description

Participants with intermediate-risk, early-stage HR+/HER2- breast cancer will be enrolled in a prospective, single-arm, multicenter phase II study. Circulating tumor DNA (ctDNA) surveillance will be performed using the Signater Genome assay, which is customized for each participant from archived tumor and matched normal DNA to detect up to 64 tumor-specific variants in plasma. Participants who are ctDNA positive at baseline will start CDK4/6 inhibitor therapy along with hormone therapy. Those who are ctDNA negative will continue hormone therapy with ctDNA testing every three months. If ctDNA becomes positive during surveillance, participants will first undergo staging to rule out distant disease before beginning CDK4/6 inhibitor therapy in addition to hormone therapy. All participants will be followed for up to nine years to assess cancer outcomes. Four-year outcomes will be compared to historical controls from the NataLEE trial to evaluate whether ctDNA-guided timing maintains efficacy while reducing unnecessary treatment.

Conditions

• Breast Neoplasms
• Carcinoma, Ductal, Breast
• Receptors, Estrogen (for ER-positive Requirement)

Interventions

Type	Name	Description
DEVICE	ctDNA-Guided Treatment Strategy	Circulating tumor DNA testing using Signatera Genome assay is performed every 3 months for up to 4 years to guide timing of CDK4/6 inhibitor initiation. Participants with positive ctDNA results initiate CDK4/6 inhibitor therapy (ribociclib or abemaciclib) plus standard endocrine therapy for a minimum of 2 years. Participants with negative ctDNA results continue endocrine therapy alone with ongoing surveillance. CDK4/6 inhibitor selection and endocrine therapy regimen per the physician's choice following standard-of-care guidelines.

Timeline

• Start date: 2026-03-24
• Primary completion: 2037-11-15
• Completion: 2037-12-30
• First posted: 2025-10-09
• Last updated: 2026-04-08

Locations

39 sites across 1 country: United States

Regulatory

• FDA-regulated device study