A Trial Using ARV-471 or Anastrozole in Post-Menopausal Women With Breast Cancer Prior to Surgery
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT05549505
- Lead Sponsor
- Arvinas Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 152
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ARV-471 monotherapy Surgical resection of breast tumor ARV-471 taken once daily until surgical resection Anastrozole monotherapy Surgical resection of breast tumor Anastrozole 1mg taken once daily until surgical resection ARV-471 monotherapy ARV-471 ARV-471 taken once daily until surgical resection Anastrozole monotherapy Anastrozole Anastrozole 1mg taken once daily until surgical resection
- Primary Outcome Measures
Name Time Method Evaluate the effects of ARV-471 and anastrozole, respectively, on Ki-67 expression in tumors after 2 weeks of treatment 2 weeks Percent change in Ki-67 expression between baseline and C1D15 tumor biopsies
- Secondary Outcome Measures
Name Time Method Evaluate the safety/tolerability of ARV-471 and anastrozole, respectively From signing of consent to minimum of 30 days after last administration of study drug Incidence of all adverse events, serious adverse events, and adverse events leading to study drug discontinuation
Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic stage) Approximately 5.5 months Pathologic stage at the time of surgical resection
Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic complete response rate) Approximately 5.5 months pathologic complete response rate at the time of surgical resection
Evaluate the pathological response of ARV-471 and anastrozole, respectively (modified Pre-operative Endocrine Prognostic Index score) Approximately 5.5 months modified Pre-operative Endocrine Prognostic Index score at the time of surgical resection
Evaluate the clinical response of ARV-471 and anastrozole, respectively (breast conserving surgery rate) Approximately 5.5 months rates of breast conserving surgery
Evaluate the clinical response of ARV-471 and anastrozole, respectively (radiographic response) Approximately 5 months radiographical response rate in the primary tumor during cycle 6
Evaluate the clinical response of ARV-471 and anastrozole, respectively (caliper-based response) Approximately 5 months Best percentage change from baseline up to C6D1 in caliper measurement of the primary tumor
Trial Locations
- Locations (1)
Clinical Trial Site
🇪🇸Zaragoza, Spain