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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05549505
• Other study ID #: ARV-471-BC-201
• Secondary ID: C4891025
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 15, 2023
• Est. completion date: August 15, 2024

Study information

• Verified date: January 2024
• Source: Arvinas Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is a Phase 2 neoadjuvant study evaluating ARV-471 or anastrozole in post-menopausal women with ER+/HER2- localized breast cancer.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 152
• Est. completion date: August 15, 2024
• Est. primary completion date: July 15, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• ARV-471
tablets
• Anastrozole
1mg tablet

Procedure:
• Surgical resection of breast tumor
Participants will have surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days)

Locations

Country	Name	City	State
Georgia	Clinical Trial Site	Batumi
Georgia	Clinical Trial Site	Tbilisi
Georgia	Clinical Trial Site	Tbilisi
Georgia	Clinical Trial Site	Tbilisi
Germany	Clinical Trial Site	Augsburg
Germany	Clinical Trial Site	Berlin
Germany	Clinical Trial Site	Bonn
Germany	Clinical Trial Site	Bottrop
Germany	Clinical Trial Site	Chemnitz
Germany	Clinical Trial Site	Dresden
Germany	Clinical Trial Site	Erlangen
Germany	Clinical Trial Site	Essen
Germany	Clinical Trial Site	Essen
Germany	Clinical Trial Site	Esslingen
Germany	Clinical Trial Site	Mannheim
Germany	Clinical Trial Site	Paderborn
Spain	Clinical Trial Site	Alicante
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Castelló
Spain	Clinical Trial Site	Córdoba
Spain	Clinical Trial Site	Granada
Spain	Clinical Trial Site	Granada
Spain	Clinical Trial Site	La Coruna	Galicia
Spain	Clinical Trial Site	Lleida
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Manresa
Spain	Clinical Trial Site	San Cristobal de La laguna	Santa Cruz De Tenerife
Spain	Clinical Trial Site	Sevilla
Spain	Clinical Trial Site	Sevilla
Spain	Clinical Trial Site	Valencia
Spain	Clinical Trial Site	Valencia
Spain	Clinical Trial Site	Zaragoza
United States	Clinical Trial Site	Fort Lauderdale	Florida
United States	Clinical Trial Site	Fort Myers	Florida
United States	Clinical Trial Site	Iowa City	Iowa
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	Orlando	Florida
United States	Clinical Trial Site	Saint Louis	Missouri
United States	Clinical Trial Site	Springdale	Arkansas
United States	Clinical Trial Site	Springfield	Massachusetts
United States	Clinical Trial Site	Tacoma	Washington
United States	Clinical Trial Site	Torrance	California
United States	Clinical Trial Site	Van Nuys	California
United States	Clinical Trial Site	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Arvinas Inc.	Pfizer

Countries where clinical trial is conducted

United States,  Georgia,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the effects of ARV-471 and anastrozole, respectively, on Ki-67 expression in tumors after 2 weeks of treatment	Percent change in Ki-67 expression between baseline and C1D15 tumor biopsies	2 weeks
Secondary	Evaluate the safety/tolerability of ARV-471 and anastrozole, respectively	Incidence of all adverse events, serious adverse events, and adverse events leading to study drug discontinuation	From signing of consent to minimum of 30 days after last administration of study drug
Secondary	Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic stage)	Pathologic stage at the time of surgical resection	Approximately 5.5 months
Secondary	Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic complete response rate)	pathologic complete response rate at the time of surgical resection	Approximately 5.5 months
Secondary	Evaluate the pathological response of ARV-471 and anastrozole, respectively (modified Pre-operative Endocrine Prognostic Index score)	modified Pre-operative Endocrine Prognostic Index score at the time of surgical resection	Approximately 5.5 months
Secondary	Evaluate the clinical response of ARV-471 and anastrozole, respectively (breast conserving surgery rate)	rates of breast conserving surgery	Approximately 5.5 months
Secondary	Evaluate the clinical response of ARV-471 and anastrozole, respectively (radiographic response)	radiographical response rate in the primary tumor during cycle 6	Approximately 5 months
Secondary	Evaluate the clinical response of ARV-471 and anastrozole, respectively (caliper-based response)	Best percentage change from baseline up to C6D1 in caliper measurement of the primary tumor	Approximately 5 months