A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+ / HER2- Early Breast Cancer

A phase III multi-center, randomized, open-label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+ / HER2- Early Breast Cancer

Inclusion Criteria

• Patient is ≥ 18 years-old at the time of PICF signature
• Patient is female with known menopausal status at the time of PICF signature or initiation of adjuvant ET (whichever occurs earlier), or male.
• Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis within 18 months prior to randomization.
• Patient has breast cancer that is positive for ER and/or PgR
• Patient has HER2-negative breast cancer
• Patient has available archival tumor tissue from the surgical specimen
• 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: anatomic stage group II or III
• If indicated, patient has completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines
• If indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines
• Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Patient has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for 5 years

Exclusion Criteria

• Patient has received any CDK4/6 inhibitor
• Patient has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within the last 2 years prior to PICF signature
• Patient has received prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin, or 900 mg/m² or more for epirubicin. Patient with a known hypersensitivity to any of the excipients of ribociclib and/or ET
• 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.
• Patient is concurrently using other anti-neoplastic therapy with the exception of adjuvant ET
• Patient has had major surgery, chemotherapy or radiotherapy within 14 days prior to randomization
• Patient has not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies
• Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before PICF signature
• Patient has known HIV infection, Hepatitis B or C infection
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
• Patient is currently receiving any of the following substances within 7 days before randomization - Concomitant medications, herbal supplements, and/or fruits that are known as strong inhibitors or inducers of CYP3A4/5 or Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
• is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment
• Patient has impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol
• Patient participated in another interventional study and received treatment with an investigational product (or used an investigational device) within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer.
• Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial

Lead Organization
Novartis Pharmaceuticals Corporation