arv-471 in combination with everolimus for the treatment of advanced or metastatic er+, her2- breast cancer

Conditions: Breast Cancer

Summary: a phase 1b study to assess the combination of arv-471 and everolimus in participants with advanced or metastatic er+/her2- breast cancer.

this is a phase 1b study to assess the safety and tolerability of arv-471 in combination with everolimus in participants with estrogen receptor positive/human epidermal growth factor receptor 2 negative (er+/her2-) advanced or metastatic breast cancer, who have received a prior cdk4/6 inhibitor and endocrine therapy in the advanced/metastatic setting.

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed er+ and her2-advanced breast cancer (metastatic, recurrent, or unresectable) * women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression * measurable disease or non-measurable (evaluable) disease per recist v1.1 * received a minimum of 1 and up to 3 lines of anti-cancer therapy in the advanced/metastatic setting: must have received and progressed on (or were intolerant to) a cdk 4/6 inhibitor, either alone or in combination; must have received at least one endocrine therapy, either alone or in combination; may have received up to one line of chemotherapy * must be willing to use dexamethasone mouthwash for the prevention of everolimus-induced stomatitis * ecog performance status of 0 or 1 exclusion criteria: * untreated brain metastases or brain metastases requiring steroids above physiologic replacement doses * prior treatment with arv-471 * prior treatment targeting mtor (e.g. everolimus) * prior anticancer or investigational drug treatment within 28 days (fulvestrant) or 14 days (tamoxifen or aromatase inhibitor, or cdk 4/6 inhibitor) before the first dose of study drug * prior anticancer or investigational anticancer drug therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of study drug, except as mentioned above * any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolism * any of the following in the previous 6 months: congenital long qt syndrome, torsade de pointes, sustained ventricular tachyarrhythmia and ventricular fibrillation, left anterior hemiblock, ongoing cardiac arrythmias/dysrhythmias, atrial fibrillation * hypertension that cannot be controlled by medication (\>150/90 mmhg despite optimal medical therapy) * active, uncontrolled bacterial, fungal, or viral infection, including hepatitis b virus, hepatitis c virus, known human immunodeficiency virus (hiv), or acquired immunodeficiency syndrome (aids)-related illness * known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung function * live vaccines within 14 days before the first dose of study drug * major surgery (as defined by the investigator) within 4 weeks of first dose of study drug * radiation therapy within 4 weeks of first dose of study drug or prior irradiation to more than 25% of the bone marrow

Keywords: advanced breast cancer metastatic breast cancer mbc endocrine therapy estrogen receptor er+ human epidermal growth factor receptor 2 her2- arv-471 everolimus protac vepdegestrant