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

NCT05549505 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ARV-471-BC-201C4891025
• Study Type: interventional
• Target: 152
• Locations: 4 countries
• Sites: 49

Brief Summary

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.

Conditions

Breast Cancer

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 negative; HER2-; ARV-471; Anastrozole; Arimidex; Aromatase inhibitor; Vepdegestrant; PF-07850327

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

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

  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

  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

  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

  At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days

• Breast Conserving Surgery (BCS) Rate

  At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days

Study Arms (2)

Arm A: ARV-471 (Experimental)

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; Procedure: Surgical resection of breast tumor

Arm B: Anastrozole

ACTIVE COMPARATOR

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; Procedure: Surgical resection of breast tumor

Interventions

ARV-471 DRUG

100 mg tablet

Also known as: Vepdegestrant, PF-07850327

Arm A: ARV-471 (Experimental)

Anastrozole DRUG

1 mg tablet

Also known as: Arimidex

Arm B: Anastrozole

Surgical resection of breast tumor PROCEDURE

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

Arm A: ARV-471 (Experimental); Arm B: Anastrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arvinas Inc.: lead
• Pfizer: collaborator

Study Sites (49)

Clinical Trial Site

Springdale, Arkansas, 72762, United States

Location

Clinical Trial Site

Los Angeles, California, 90095, United States

Location

Clinical Trial Site

Torrance, California, 90505, United States

Location

Clinical Trial Site

Van Nuys, California, 91405, United States

Location

Clinical Trial Site

Fort Lauderdale, Florida, 33308, United States

Location

Clinical Trial Site

Fort Myers, Florida, 33901, United States

Location

Clinical Trial Site

Orlando, Florida, 32806, United States

Location

Clinical Trial Site

West Palm Beach, Florida, 33401, United States

Location

Clinical Trial Site

Iowa City, Iowa, 52242, United States

Location

Clinical Trial Site

Springfield, Massachusetts, 01199, United States

Location

Clinical Trial Site

St Louis, Missouri, 63110, United States

Location

Clinical Trial Site

Nashville, Tennessee, 37203, United States

Location

Clinical Trial Site

Tacoma, Washington, 98405, United States

Location

Clinical Trial Site

Batumi, 6000, Georgia

Location

Clinical Trial Site

Tbilisi, 0112, Georgia

Location

Clinical Trial Site

Tbilisi, 0144, Georgia

Location

Clinical Trial Site

Tbilisi, 0159, Georgia

Location

Clinical Trial Site

Augsburg, 86156, Germany

Location

Clinical Trial Site

Berlin, 13125, Germany

Location

Clinical Trial Site

Bonn, 53111, Germany

Location

Clinical Trial Site

Bottrop, 46236, Germany

Location

Clinical Trial Site

Chemnitz, 09116, Germany

Location

Clinical Trial Site

Dresden, 01307, Germany

Location

Clinical Trial Site

Erlangen, 91054, Germany

Location

Clinical Trial Site

Essen, 451136, Germany

Location

Clinical Trial Site

Essen, 45147, Germany

Location

Clinical Trial Site

Esslingen am Neckar, 73730, Germany

Location

Clinical Trial Site

Mannheim, 68167, Germany

Location

Clinical Trial Site

Paderborn, 33098, Germany

Location

Clinical Trial Site

A Coruña, Galicia, 15006, Spain

Location

Clinical Trial Site

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Clinical Trial Site

Alicante, 03010, Spain

Location

Clinical Trial Site

Barcelona, 08025, Spain

Location

Clinical Trial Site

Barcelona, 08036, Spain

Location

Clinical Trial Site

Barcelona, 08916, Spain

Location

Clinical Trial Site

Castelló, 12002, Spain

Location

Clinical Trial Site

Córdoba, 14004, Spain

Location

Clinical Trial Site

Granada, 18005, Spain

Location

Clinical Trial Site

Granada, 18014, Spain

Location

Clinical Trial Site

Lleida, 25198, Spain

Location

Clinical Trial Site

Madrid, 28034, Spain

Location

Clinical Trial Site

Madrid, 28040, Spain

Location

Clinical Trial Site

Madrid, 28922, Spain

Location

Clinical Trial Site

Manresa, 08243, Spain

Location

Clinical Trial Site

Seville, 41009, Spain

Location

Clinical Trial Site

Seville, 41013, Spain

Location

Clinical Trial Site

Valencia, 46009, Spain

Location

Clinical Trial Site

Valencia, 46010, Spain

Location

Clinical Trial Site

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Arvinas Estrogen Receptor, Inc.
• Organization: Arvinas Estrogen Receptor, Inc

clinicaltrialsARV-471@arvinas.com

475-345-3366

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 22, 2022
• Study Start: February 15, 2023
• Primary Completion: July 13, 2024
• Study Completion: July 25, 2024
• Last Updated: August 29, 2025
• Results First Posted: August 29, 2025

Record last verified: 2025-08

Locations

US (13); GE (4); DE (12); ES (20)