A Phase 1b Trial of ARV-471 in Combination With Everolimus in Patients With ER+, HER2- Advanced or Metastatic Breast Cancer

ARV-471-mBC-102

A phase 1b study to assess the combination of ARV-471 and everolimus in participants with advanced or metastatic ER+/HER2- breast cancer.

2022-09-08

2024-05-30

2024-11-30

Active (not recruiting)

Early phase I

32

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

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2024-01-22