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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anastrozole; Drug: ARV-471; Procedure: Surgical resection of breast tumor

Detailed Description

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
• Enrollment (Actual): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Batumi, Georgia, 6000
    • Clinical Trial Site
  • Tbilisi, Georgia, 0112
    • Clinical Trial Site
  • Tbilisi, Georgia, 0144
    • Clinical Trial Site
  • Tbilisi, Georgia, 0159
    • Clinical Trial Site
• Germany
  • Augsburg, Germany, 86156
    • Clinical Trial Site
  • Berlin, Germany, 13125
    • Clinical Trial Site
  • Bonn, Germany, 53111
    • Clinical Trial Site
  • Bottrop, Germany, 46236
    • Clinical Trial Site
  • Chemnitz, Germany, 09116
    • Clinical Trial Site
  • Dresden, Germany, 01307
    • Clinical Trial Site
  • Erlangen, Germany, 91054
    • Clinical Trial Site
  • Essen, Germany, 45147
    • Clinical Trial Site
  • Essen, Germany, 451136
    • Clinical Trial Site
  • Esslingen am Neckar, Germany, 73730
    • Clinical Trial Site
  • Mannheim, Germany, 68167
    • Clinical Trial Site
  • Paderborn, Germany, 33098
    • Clinical Trial Site
• Spain
  • Alicante, Spain, 03010
    • Clinical Trial Site
  • Barcelona, Spain, 08036
    • Clinical Trial Site
  • Barcelona, Spain, 08025
    • Clinical Trial Site
  • Barcelona, Spain, 08916
    • Clinical Trial Site
  • Castelló, Spain, 12002
    • Clinical Trial Site
  • Córdoba, Spain, 14004
    • Clinical Trial Site
  • Granada, Spain, 18014
    • Clinical Trial Site
  • Granada, Spain, 18005
    • Clinical Trial Site
  • Lleida, Spain, 25198
    • Clinical Trial Site
  • Madrid, Spain, 28040
    • Clinical Trial Site
  • Madrid, Spain, 28034
    • Clinical Trial Site
  • Madrid, Spain, 28922
    • Clinical Trial Site
  • Manresa, Spain, 08243
    • Clinical Trial Site
  • Seville, Spain, 41009
    • Clinical Trial Site
  • Seville, Spain, 41013
    • Clinical Trial Site
  • Valencia, Spain, 46009
    • Clinical Trial Site
  • Valencia, Spain, 46010
    • Clinical Trial Site
  • Zaragoza, Spain, 50009
    • Clinical Trial Site
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Clinical Trial Site
  • Santa Cruz De Tenerife
    • San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Clinical Trial Site
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Clinical Trial Site
  • California
    • Los Angeles, California, United States, 90095
      • Clinical Trial Site
    • Torrance, California, United States, 90505
      • Clinical Trial Site
    • Van Nuys, California, United States, 91405
      • Clinical Trial Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Clinical Trial Site
    • Fort Myers, Florida, United States, 33901
      • Clinical Trial Site
    • Orlando, Florida, United States, 32806
      • Clinical Trial Site
    • West Palm Beach, Florida, United States, 33401
      • Clinical Trial Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Clinical Trial Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Clinical Trial Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Clinical Trial Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Trial Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: ARV-471 (Experimental); Participants received 200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than Cycle 6 Day 18 [C6D18] + 14 days).	Drug: ARV-471; 100 mg tablet; Other Names: PF-07850327; Vepdegestrant; Procedure: Surgical resection of breast tumor; Surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days)
Active Comparator: Arm B: Anastrozole; Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days).	Drug: Anastrozole; 1 mg tablet; Other Names: Arimidex; Procedure: Surgical resection of breast tumor; Surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline (during screening, prior to Day 1) and Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From signing of consent to minimum of 30 days after last administration of study drug (up to approximately 6.5 months)
Pathologic Stage at the Time of Surgical Resection	Local pathological assessment of the tissue from surgical resection (performed after approximately 5.5 months of treatment), at minimum, included pathologic stage (ypT and ypN stage) as described in the Laboratory Manual. Participants were analysed based on the current American Joint Committee on Cancer (AJCC) staging system as follows: Pathologic Tumor - post-neoadjuvant therapy pathologic tumor categorization (ypT): (ypTx, ypT0, ypTis, ypT1mi, ypT1a, ypT1b, ypT1c, ypT2, ypT3, ypT4a, ypT4b, ypT4c).; Pathological Lymph Nodes - post-neoadjuvant therapy pathologic node categorization (ypN): (ypNX, ypN0, ypN0(i+), ypN0(mol+), ypN1, ypN1mi, ypN1a, ypN1b, ypN1c, ypN2, ypN2a, ypN2b, ypN3, ypN3a, ypN3b, ypN3c).; ypT0 / ypN0 indicates no evidence of disease and the progressive grades indicate increasing size of tumor and increasing area of lymph node involvement respectively and ypTx/ypNX indicates non-measurable disease.	At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days
Pathological Complete Response(pCR) Rate at the Time of Surgical Resection	pCR is defined as no invasive cancer in the breast and sampled axillary lymph nodes following completion of neoadjuvant systemic therapy (ie, Pathologic Tumor - ypT = ypT0 or ypTis, and Pathologic Lymph Nodes - ypN = ypN0 in the current American Joint Committee on Cancer (AJCC) staging system). pCR rate is the percentage of participants with pCR.	At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days
Number of Participants With Modified Preoperative Endocrine Prognostic Index (mPEPI) Score of 0 at the Time of Surgical Resection	Modified Pre-operative Endocrine Prognostic Index (mPEPI) score is an investigational prognostic tool used to predict the risk of breast cancer recurrence. It will be derived from factors assigned a numerical score following Neoadjuvant endocrine treatment (NET). The factors include pathologic tumor size, and lymph node status and Ki67 expression in the surgical specimen. Total mPEPI score (mPEPI_T) per participant is the sum of mPEPI score of each factor. mPEPI score of 0 indicates Pathological tumor size T1-T2, no lymph nodes and Ki67 level of 0%-2.7%, 1 indicates: Ki67 level >2.7%-7.3%, 2 indicates Ki67 level >19.7%-53.1% and 3 indicates: tumor sizeT3-T4, presence of lymph nodes and Ki67 level >53.1%.	At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days
Breast Conserving Surgery (BCS) Rate	Breast conserving surgery (BCS) Rate is the percentage of participants received breast conserving surgery.	At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days
Radiographic Response Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) in Primary Tumor During Cycle 6	The number of participants with Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE) per mRECIST calculated. CR = disappearance of all target lesions, PR is >=30% decrease in sum of diameters of target lesions, progressive disease (PD) is >=20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.	At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days
Percentage Change From Baseline at Cycle 6 Day 1 in Caliper Measurement of the Primary Tumor	The percentage change from the baseline of the primary breast tumor size in physical exam calculated in caliper measurement. Caliper-based response is the maximum percentage decrease or minimum percentage increase if there is no decrease per participant.	Baseline (Day 1) and Cycle 6 Day 1 (At Day 141), each cycle is 28 days

Collaborators and Investigators

• Sponsor: Arvinas Inc.
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Actual): July 13, 2024
• Study Completion (Actual): July 25, 2024

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Neoadjuvant; HR+; HER2-; Hormone receptor positive; Estrogen receptor positive; ER+; Arimidex; Aromatase inhibitor; Anastrozole; human epidermal growth factor receptor 2 negative; Estrogen receptor; Early breast cancer; Localized breast cancer; Untreated breast cancer; Pre-operative breast cancer; Treatment-naïve breast cancer; Hormone positive; ARV-471; Vepdegestrant; PF-07850327
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Nitriles; Triazoles; Anastrozole
• Other Study ID Numbers: ARV-471-BC-201; C4891025 (Other Identifier: Pfizer)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No