tactive-u: a study to learn about the study medicine (vepdegestrant) when given with other medicines in people with advanced or metastatic breast cancer (sub-study a)

Conditions: Breast Cancer

Summary: the purpose of this clinical trial is to learn about the safety and effects of the study medicine (called arv-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer. this study is seeking participants who have breast cancer that: * is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy * is sensitive to hormonal therapy (it is called estrogen receptor positive); and * is no longer responding to previous treatments this study is divided into separate sub-studies. for sub-study a: all participants will receive arv-471 and a medicine called abemaciclib. arv-471 will be given by mouth, at home, 1 time a day. abemaciclib will be given by mouth, at home, 2 times a day. we will examine the experiences of people receiving the study medicines. this will help us determine if the study medicines are safe and effective. participants will continue to take arv-471 and abemaciclib until their cancer is no longer responding, or side effects become too severe. they will have visits at the study clinic about every 4 weeks.

c4891006 is a sub-study from the umbrella platform, tactive-u, comprising multiple sub-studies that independently evaluate arv-471 in participants with estrogen receptor positive (er+) advanced or metastatic breast cancer (a/mbc). arv-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in er+ breast cancer.

Eligibility criteria:
inclusion criteria: * histological or cytological diagnosis of er+ and her2- advanced/metastatic breast cancer 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 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1 line of any cdk4/6 inhibitor-based regimen is required (independent of the setting eg, adjuvant or advanced/metastatic) * at least 1 measurable lesion as defined by recist v1.1. * ecog ps ≤1. exclusion criteria: * visceral crisis at risk of life-threatening complications in the short term * known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions. * 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 the study. * history of any other tumor 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. * inflammatory breast cancer * impaired cardiovascular function or clinically significant cardiovascular diseases * concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of cyp3a and drugs known to predispose to torsade de pointes or qt interval prolongation. * renal impairment, not adequate liver function and/or bone marrow function * known active infection

Keywords: tactive-u umbrella study protac metastatic breast cancer