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

Arvinas Inc.152 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

152

Conditions

Breast Cancer

Interventions

ARV-471DRUG

100 mg tablet

AnastrozoleDRUG

1 mg tablet

Surgical resection of breast tumorPROCEDURE

Surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days)

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (49)

Outcomes

Primary Outcomes

Percent Reduction in Ki-67 Expression From Baseline to Day 15 in Tumor Biopsies

Tumor biopsy Ki-67 expression (% of tumor cells that are positive for Ki-67) at baseline and Cycle 1 Day 15 (C1D15) was collected. Ki-67 expression was assessed by immunohistochemical staining in a central laboratory. The log-transformed Ki-67 after approximately 2 weeks of treatment as a percentage of the baseline value, ie, the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline was modelled using a generalized linear model (GLM) with both stratification factors (ie, baseline Ki-67 score and the tumor size) and treatment as co-variates. The treatment effects were back transformed into geometric means and their Confidence Intervals. The percent change, in other words, relative reduction, of Ki-67 after 2 weeks of treatment is reported as the complement of the ratio between the Ki-67 measurement from C1D15 and baseline, that is 100% × (1 - geometric mean ratio between Ki-67 at C1D15 and Ki-67 at baseline).

Time frame: Baseline (during screening, prior to Day 1) and Day 15

Secondary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Study Drug Discontinuation

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE is an AE that emerges or worsens on/after the first dose of ARV-471/Anastrozole to 30 days after the last administration of the study intervention (ie, study drug treatment or surgical resection, whichever occurs last).

Time frame: From signing of consent to minimum of 30 days after last administration of study drug (up to approximately 6.5 months)

Data from ClinicalTrials.gov

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Clinical Trial Site

Springdale, Arkansas, United States

Clinical Trial Site

Los Angeles, California, United States

Clinical Trial Site

Torrance, California, United States

Clinical Trial Site

Van Nuys, California, United States

Clinical Trial Site

Fort Lauderdale, Florida, United States

Clinical Trial Site

Fort Myers, Florida, United States

Clinical Trial Site

Orlando, Florida, United States

Clinical Trial Site

West Palm Beach, Florida, United States

Clinical Trial Site

Iowa City, Iowa, United States

Clinical Trial Site

Springfield, Massachusetts, United States

...and 39 more locations