SIgnatera-Guided Initiation of Adjuvant CDK4/6 Inhibitor in Intermediate Risk HR+ HER2- Breast Cancer
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.
• Signed and dated Informed Consent Form (ICF) obtained prior to any trial-specific screening procedure.
• Patient is ≥ 18 years-old at the time of ICF signature.
• Patient is female with known menopausal status at the time of initiation of adjuvant endocrine therapy (ET), or male.
• Patient with histologically confirmed unilateral and unifocal primary invasive adenocarcinoma of the breast prior to initiating adjuvant chemotherapy, if indicated, or within 6 months of initiating adjuvant endocrine therapy if chemotherapy is not indicated. Patients who receive neoadjuvant endocrine therapy or chemotherapy are allowed to enroll.
• Patient has breast cancer that is positive for ER and/or PR according to the local laboratory as determined on the most recently analyzed tissue sample.
• Patient has HER2-negative breast cancer defined as a negative in situ hybridization test (FISH, CISH, or SISH) or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (ISH) test is required to confirm the HER2-negative status.
• Patient has available archival tumor tissue from the diagnostic biopsy or surgical specimen, for submission to a central laboratory for Signatera testing (unless Signatera Genome clinical testing has already been performed).
• Patient after surgical resection where tumor was removed completely (i.e., negative microscopic margins on final pathology) and have Anatomic Stage II that is eligible for adjuvant CDK4/6 inhibitors. The criteria to be eligible for adjuvant CDK4/6 inhibitors include N1, or N0 with T3 or T2 with either G3, or G2 with Ki67 greater or equal to 20% or high genomic risk score.
• Notes:
‣ Patients who received neoadjuvant treatment must meet the criteria for stage, grade, Ki67 in any presurgical staging/sample and/or in the surgical specimen.
‣ Categorization into the AJCC 8th edition Anatomic Stage Groups requires determination of the T, N and M categories. ALND can be omitted.
• Patient has no contraindication to adjuvant ET and is planned to be treated with ET for 5 years (since enrollment date) or more.
⁃ Provider and patient must be agreeable to initiate CDK4/6 inhibitors only upon ctDNA detection.
⁃ Patient may have received up to 6 months of standard adjuvant ET at the time of enrollment and any amount of neoadjuvant endocrine therapy.
⁃ Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
⁃ Patient must not have a clinical contraindication to ribociclib or abemaciclib.
⁃ Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
⁃ Women of childbearing potential (CBP) must have a confirmed negative serum pregnancy test within 14 days prior to enrollment.
⁃ Women of reproductive potential should be advised of the potential risk of CDK4/6 inhibitors to a fetus, and use effective contraception during CDK 4/6 inhibitor therapy.