ctDNA-Guided Chemotherapy Omission With Ribociclib Plus Endocrine Therapy in HR-Positive/HER2-Negative Breast Cancer

A Multicenter, Open-label, Randomized Controlled Clinical Study Comparing the Efficacy and Safety of ctDNA-guided Ribociclib Plus Endocrine Therapy Versus Chemotherapy Followed by Ribociclib Plus Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer

This study is a prospective, multicenter, open-label, randomized controlled clinical trial designed to determine whether ribociclib plus endocrine therapy (ET) is non-inferior to adjuvant chemotherapy followed by ribociclib plus ET in patients with circulating tumor DNA (ctDNA)-negative, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer.

This study is a prospective, multicenter, open-label, randomized controlled clinical trial designed to determine whether ribociclib plus endocrine therapy (ET) is non-inferior to adjuvant chemotherapy followed by ribociclib plus ET in patients with circulating tumor DNA (ctDNA)-negative, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer.

Patients with HR+/HER2- early breast cancer who have undergone definitive surgery will be enrolled and must undergo ctDNA-MRD analysis within 4 weeks after surgery. Patients who are ctDNA negative will be randomly assigned (1:1) to two study groups, according to stratification factors: menopausal status (premenopausal vs. postmenopausal). The experimental group will receive ribociclib plus aromatase inhibitor (AI) or ovarian function suppression (OFS), while the control group will receive chemotherapy followed by ribociclib plus AI or OFS. The safety and efficacy of each group will be assessed through ctDNA nagative rate, invasive disease free survival (iDFS), and adverse effects (AE) as graded by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 and patient reported outcome (PRO).

Inclusion Criteria:

1. Signed and dated Patient Informed Consent Form (PICF) obtained prior to any trial-specific screening procedure
2. Patient is female with known menopausal status at the time of randomization
3. Patient is ≥ 18 and ≤70 years-old at the time of PICF signature.
4. Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis
5. Patient has breast cancer that is positive for ER and/or PgR as determined on the most recently analyzed tissue sample
6. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample).
7. Patient after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories:

1) T0-2N1, 2) T3-4N0, 3) T2N0 meeting the following criteria:

1. histological Grade 3,
2. histological Grade 2 with Ki-67 proliferation index ≥20% or/and high genomic risk 8. Eligible to adjuvant chemotherapy per investigator's decision (Based on clinicopathological findings or genomic assay results) 9. ECOG Performance Status of 0 or 1 10. ctDNA-MRD negative within 4 weeks post-surgery 11. Adequate hematological, renal, and hepatic function

Exclusion Criteria:

1. Prior neoadjuvant or adjuvant systemic treatment (including chemotherapy, targeted therapy, or endocrine therapy) for breast cancer
2. Bilateral breast cancer
3. Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery
4. Patient has other active malignancies within the past 2 years
5. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial
6. Patient has impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments
7. Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to a NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 5.0 Grade ≤ 1 at day of randomization
8. Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational drug(s) (whichever is longer), or participation in any other type of medical research judged not to be scientifically or medically compatible with this trial