TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer

Inclusion Criteria

• Histologically and/or cytologically confirmed diagnosis of Estrogen Receptor-Positive (ER+) and/or Progesterone Receptor-Positive (PR+) breast cancer by local laboratory.
• Human Epidermal growth factor Receptor 2 Negative (HER2-) breast cancer defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative In Situ Hybridization (Fluorescence [FISH], Chromogenic [CISH], or Silver [SISH]) test is required by local laboratory testing.
• Participants are allowed (but not required) to have up to two lines of prior chemotherapy regimens in the metastatic setting for the dose expansion phase. For the dose escalation cohort, up to three previous lines of chemotherapy in the metastatic setting is acceptable.
• Measurable disease, i.e., at least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria only *for expansion cohorts.
• For *escalation cohorts, bone only disease is allowed. For expansion cohorts, there must be measurable disease as stated above.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.
• Written informed consent must be obtained prior to any screening procedures and according to local guidelines.
• Adequate bone marrow and organ function.
• Must be able to swallow ribociclib and Tamoxifen capsules/tablets.
• Pre-Menopausal Women Eligibility: 1) Pre-menopausal women who received adjuvant Aromatase Inhibitor and Ovarian Suppression (AI + OS) in the adjuvant setting and completed at least 12 months of hormonal therapy. 2) Pre-menopausal women with de novo metastatic disease are eligible if they have had no prior endocrine therapy. 3) Pre-menopausal women who have not received Tamoxifen in the metastatic setting, but have received up to two lines of chemotherapy.
• Post-Menopausal Women and Men Eligibility: 1) Post-menopausal women or men who have progressed on first-line or second line therapy with an aromatase inhibitor in the metastatic setting. 2) Post-menopausal women or men who have recurred while on or after completion of adjuvant treatment with aromatase inhibitors (they have completed at least one year of AI in the adjuvant setting before progression on AI). 3) Post-menopausal women or men who are not considered candidates for treatment with an aromatase inhibitory by their oncologist, patients not willing to go on AI, or patients who were intolerant to AI.
• Post-menopausal women or men are allowed (but not required) to have up to two lines of prior chemotherapy regimens in the metastatic setting for the dose expansion phase . For the dose escalation cohort, up to three previous lines of chemotherapy in the metastatic setting is acceptable.

Exclusion Criteria

• Potential participants with inflammatory breast cancer.
• Prior CDK 4/6 inhibitor exposure.
• Have received Tamoxifen in the metastatic setting (for more than 30 days) or has progressed while on Tamoxifen in the adjuvant setting.
• Known hypersensitivity to ribociclib or excipients of tamoxifen.
• A concurrent malignancy or malignancy within 3 years of starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Central nervous system (CNS) involvement unless specific criteria are met.
• Impairment of Gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known history of HIV infection (testing not mandatory).
• 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 study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or