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

Sponsor

Arvinas Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05549505

Collaborator

Pfizer (Industry)

150

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: ARV-471 Drug: Anastrozole Procedure: Surgical resection of breast tumor	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARV-471 monotherapy ARV-471 taken once daily until surgical resection	Drug: ARV-471 tablets Procedure: Surgical resection of breast tumor Participants will have surgical resection approximately 5.5 months after starting treatment (C6D18 ± 10 days)
Active Comparator: Anastrozole monotherapy Anastrozole 1mg taken once daily until surgical resection	Drug: Anastrozole 1mg tablet Other Names: Arimidex Procedure: Surgical resection of breast tumor Participants will have surgical resection approximately 5.5 months after starting treatment (C6D18 ± 10 days)

Arm

Intervention/Treatment

Experimental: ARV-471 monotherapy

ARV-471 taken once daily until surgical resection

Drug: ARV-471

tablets

Procedure: Surgical resection of breast tumor

Participants will have surgical resection approximately 5.5 months after starting treatment (C6D18 ± 10 days)

Active Comparator: Anastrozole monotherapy

Anastrozole 1mg taken once daily until surgical resection

Drug: Anastrozole

1mg tablet

Other Names:

Arimidex

Procedure: Surgical resection of breast tumor

Participants will have surgical resection approximately 5.5 months after starting treatment (C6D18 ± 10 days)

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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