TACTIVE-U: An Umbrella Study to Investigate the Safety and Antitumor Activity of ARV-471 in Combination With Other Medicines in Adults With ER+ Advanced or Metastatic Breast Cancer, Sub-study B (ARV-471 and Ribociclib)

Prior treatment

• Participants with newly diagnosed brain metastases, or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 14 days prior to enrollment.
• In addition, for participants to be enrolled in the DDI Assessment Cohort(s): moderate CYP3A inhibitors and inducers are also prohibited to avoid potential impact on DDI analysis.

Other illness

• Participants with a known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
• Impaired cardiovascular function or clinically significant cardiovascular diseases.
• Renal impairment, not adequate liver function and or bone marrow function.
• Known active infection including HBV, HCV, and HIV or AIDS-related illness.

Lab values

• Concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong inducers of CYP3A, and drugs known to predispose to Torsade de Pointes or QT interval prolongation.

Age

• History of any other malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix. All other malignancies must have been curatively treated and with no evidence of disease for >3 years. Participants with inflammatory breast cancer are excluded.

Other

• Participants in visceral crisis at risk of life-threatening complications in the short term.

• Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening.
• Histological or cytological diagnosis of ER+ and HER2- A/MBC that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy)
• Prior anticancer therapies: - At least one and no more than to 2 lines of prior therapies for advanced/metastatic disease - 1 and only 1, line of any prior CDK4/6 inhibitor-based regimen is required (independent of the setting eg, adjuvant or advanced/metastatic). If prior CDK4/6 inhibitor was permanently discontinued due to an adverse event, the participant will not be eligible. If prior CDK4/6 inhibitor required dose reductions due to an adverse event, refer to Section 6.9.1 for the eligibility evaluation.
• Participants must have at least 1 measurable lesion as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.