Clinical Research Directory

Inclusion Criteria: Age ≥ 18 years old. Patients with one of the following indications: Phase I: HR+/HER2- aBC with disease progression on or following at least one line of hormone-based therapy in combination with a CDK4/6i and at least one additional line of systemic therapy for metastatic disease. Histologically and/or cytologically confirmed diagnosis of locally advanced or metastatic cancer with a CCNE1 amplification. For dose expansion only: no more than 3 prior lines of therapy for advanced or metastatic disease. Phase II: HR+/HER2- aBC with disease progression on an aromatase inhibitor or tamoxifen in combination with a CDK4/6 inhibitor for unresectable/metastatic disease with no more than 2 lines of endocrine therapy. Measurable disease as determined by RECIST v1.1. BC only: If no measurable disease is present, then at least one predominantly lytic bone lesion must be present that can be accurately assessed at baseline and is suitable for repeated assessment. Exclusion Criteria: Previous treatment with a CDK2 inhibitor at any time. Patients with inadequate bone marrow and/or organ functions with out-of-range laboratory values. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including MI, CABG, long QT syndrome, or risk factors for TdP. Presence of symptomatic CNS metastases or CNS metastases that require local therapy or increasing doses of corticosteroids within 2 weeks prior to study entry. For the combination treatment: Patients with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine-based therapy. Patients who could not tolerate the prescribed dose of ribociclib during a previous course of treatment, requiring dose reduction or permanent discontinuation due to adverse events. For patients with BC: Patient is concurrently using hormone replacement therapy. WOCBP who are unwilling to use highly effective contraception methods, pregnant or nursing women. Other protocol-defined inclusion/exclusion criteria may apply.