Clinical trial NCT05549505: A Trial Using ARV-471 or Anastrozole in Post-Menopausal Women With Breast Cancer Prior to Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
HER2-
ARV-471
Anastrozole
Arimidex
Aromatase inhibitor
Vepdegestrant
Lead sponsor: Arvinas Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2022-09-22
Enrollment: 152
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the effects of ARV-471 and anastrozole, respectively, on Ki-67 expression in tumors after 2 weeks of treatment
timeFrame: 2 weeks
Secondary outcomes:
measure: Evaluate the safety/tolerability of ARV-471 and anastrozole, respectively
timeFrame: From signing of consent to minimum of 30 days after last administration of study drug
measure: Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic stage)
timeFrame: Approximately 5.5 months
measure: Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic complete response rate)
timeFrame: Approximately 5.5 months
measure: Evaluate the pathological response of ARV-471 and anastrozole, respectively (modified Pre-operative Endocrine Prognostic Index score)
timeFrame: Approximately 5.5 months
measure: Evaluate the clinical response of ARV-471 and anastrozole, respectively (breast conserving surgery rate)
timeFrame: Approximately 5.5 months
measure: Evaluate the clinical response of ARV-471 and anastrozole, respectively (radiographic response)
timeFrame: Approximately 5 months
measure: Evaluate the clinical response of ARV-471 and anastrozole, respectively (caliper-based response)
timeFrame: Approximately 5 months
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Clinical Trial Site
state: Arkansas
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: Torrance
country: United States
facility: Clinical Trial Site
state: California
city: Van Nuys
country: United States
facility: Clinical Trial Site
state: California
city: Fort Lauderdale
country: United States
facility: Clinical Trial Site
state: Florida
city: Fort Myers
country: United States
facility: Clinical Trial Site
state: Florida
city: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: West Palm Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Iowa City
country: United States
facility: Clinical Trial Site
state: Iowa
city: Springfield
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Tacoma
country: United States
facility: Clinical Trial Site
state: Washington
city: Batumi
country: Georgia
facility: Clinical Trial Site
city: Tbilisi
country: Georgia
facility: Clinical Trial Site
city: Tbilisi
country: Georgia
facility: Clinical Trial Site
city: Tbilisi
country: Georgia
facility: Clinical Trial Site
city: Augsburg
country: Germany
facility: Clinical Trial Site
city: Berlin
country: Germany
facility: Clinical Trial Site
city: Bonn
country: Germany
facility: Clinical Trial Site
city: Bottrop
country: Germany
facility: Clinical Trial Site
city: Chemnitz
country: Germany
facility: Clinical Trial Site
city: Dresden
country: Germany
facility: Clinical Trial Site
city: Erlangen
country: Germany
facility: Clinical Trial Site
city: Essen
country: Germany
facility: Clinical Trial Site
city: Essen
country: Germany
facility: Clinical Trial Site
city: Esslingen
country: Germany
facility: Clinical Trial Site
city: Mannheim
country: Germany
facility: Clinical Trial Site
city: Paderborn
country: Germany
facility: Clinical Trial Site
city: La Coruna
country: Spain
facility: Clinical Trial Site
state: Galicia
city: San Cristobal de La laguna
country: Spain
facility: Clinical Trial Site
state: Santa Cruz De Tenerife
city: Alicante
country: Spain
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Castelló
country: Spain
facility: Clinical Trial Site
city: Córdoba
country: Spain
facility: Clinical Trial Site
city: Granada
country: Spain
facility: Clinical Trial Site
city: Granada
country: Spain
facility: Clinical Trial Site
city: Lleida
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Manresa
country: Spain
facility: Clinical Trial Site
city: Sevilla
country: Spain
facility: Clinical Trial Site
city: Sevilla
country: Spain
facility: Clinical Trial Site
city: Valencia
country: Spain
facility: Clinical Trial Site
city: Valencia
country: Spain
facility: Clinical Trial Site
city: Zaragoza
country: Spain
facility: Clinical Trial Site
Study officials:
References: