A Trial Using ARV-471 or Anastrozole in Post-Menopausal Women With Breast Cancer Prior to Surgery

An Open-label, Randomized, Non-comparative Phase 2 Study of ARV-471 or Anastrozole in Post-menopausal Women With ER+/HER2- Breast Cancer in the Neoadjuvant Setting

This trial is a Phase 2 neoadjuvant study evaluating ARV-471 or anastrozole in post-menopausal women with estrogen receptor positive/ human epidermal growth factor receptor 2 (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.

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 immunohistochemistry (IHC) per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
  • 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.

• Eastern Cooperative Oncology Group (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).
• corrected QT (Fridericia method) (QTcF) > 470 msec.
• Active, uncontrolled bacterial, fungal or viral infection, including (but not limited to) hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (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.