a trial using arv-471 or anastrozole in post-menopausal women with breast cancer prior to surgery

Conditions: Breast Cancer

Summary: this trial is a phase 2 neoadjuvant study evaluating arv-471 or anastrozole in post-menopausal women with er+/her2- localized breast cancer.

this is a phase 2, open-label, randomized, non-comparative proof of concept study of arv-471 or anastrozole in participants with er+/her2- breast cancer amenable to definitive surgical resection. the main goal of this study is to evaluate the biological activity of arv-471 and anastrozole, respectively.

Eligibility criteria:
inclusion criteria: * post-menopausal females ≥ 18 years * histologically or cytologically confirmed er+ and her2- breast cancer (per local assessment). er and her2 status must be documented: * er+ disease, with er staining of ≥ 10% of tumor cell nuclei by ihc per asco/cap guidelines (allison 2020). * her2- disease by either ihc or in situ hybridization per asco/cap guidelines * ki-67 score ≥ 5%, analyzed locally * clinical t1c-t4c, n0-n2, m0 breast cancer amenable to definitive surgical resection, without bilateral breast ductal carcinoma in situ or invasive breast cancer * the primary tumor must be at least 1.5 cm by imaging * ecog performance status of 0 or 1 willingness to undergo a screening biopsy, an on-treatment biopsy and surgical resection exclusion criteria: * any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or cervical carcinoma in situ * any of the following in the previous 6 months: myocardial infarction; severe unstable angina; coronary/peripheral artery bypass graft; symptomatic congestive heart failure (new york heart association class iii or iv); 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 (bifascicular block); ongoing cardiac dysrhythmias of nci ctcae ≥ grade 2; atrial fibrillation of any grade (≥ grade 2 in the case of asymptomatic lone atrial fibrillation) * qtcf \> 470 msec * active, uncontrolled bacterial, fungal or viral infection, including hbv, hcv, and hiv or aids-related illness * active inflammatory gastrointestinal disease, chronic diarrhea, known uncontrolled diverticular disease, or previous gastric resection or lap band surgery * cirrhosis meeting criteria for child pugh b and c * prior treatment for breast cancer including systemic therapy (eg, chemotherapy, hormonal therapy), radiation, surgery, or any investigational agents * any live vaccines within 14 days of planned start of first dose of study drug. * major surgery (as defined by the investigator) within four weeks of first dose of study drug

Keywords: early breast cancer localized breast cancer untreated breast cancer pre-operative breast cancer treatment-naïve breast cancer neoadjuvant estrogen receptor estrogen receptor positive er+ hormone positive hormone receptor positive hr+ human epidermal growth factor receptor 2 her2- arv-471 anastrozole arimidex aromatase inhibitor vepdegestrant