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

• ClinicalTrials.gov Identifier: NCT05549505
• Recruitment Status: Recruiting
• First Posted: September 22, 2022
• Last Update Posted: January 27, 2023
• Sponsor: Arvinas Inc.
• Collaborator: Pfizer
• Information provided by (Responsible Party): Arvinas Inc.

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 (Clinical Trial)
• Estimated 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
• Estimated Study Start Date: January 2023
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: June 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 Name: 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 :

1. Evaluate the effects of ARV-471 and anastrozole, respectively, on Ki-67 expression in tumors after 2 weeks of treatment [ Time Frame: 2 weeks ]
   Percent change in Ki-67 expression between baseline and C1D15 tumor biopsies

Secondary Outcome Measures :

1. Evaluate the safety/tolerability of ARV-471 and anastrozole, respectively [ Time Frame: 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
2. Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic stage) [ Time Frame: Approximately 5.5 months ]
   Pathologic stage at the time of surgical resection
3. Evaluate the pathological response of ARV-471 and anastrozole, respectively (pathologic complete response rate) [ Time Frame: Approximately 5.5 months ]
   pathologic complete response rate at the time of surgical resection
4. Evaluate the pathological response of ARV-471 and anastrozole, respectively (modified Pre-operative Endocrine Prognostic Index score) [ Time Frame: Approximately 5.5 months ]
   modified Pre-operative Endocrine Prognostic Index score at the time of surgical resection
5. Evaluate the clinical response of ARV-471 and anastrozole, respectively (breast conserving surgery rate) [ Time Frame: Approximately 5.5 months ]
   rates of breast conserving surgery
6. Evaluate the clinical response of ARV-471 and anastrozole, respectively (radiographic response) [ Time Frame: Approximately 5 months ]
   radiographical response rate in the primary tumor during cycle 6
7. Evaluate the clinical response of ARV-471 and anastrozole, respectively (caliper-based response) [ Time Frame: Approximately 5 months ]
   Best percentage change from baseline up to C6D1 in caliper measurement of the primary tumor

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Arvinas Estrogen Receptor, Inc.; 475-345-3366; clinicaltrialsARV-471@arvinas.com

Locations

United States, Missouri

Clinical Trial Site; Recruiting

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Arvinas Inc.

Pfizer

More Information

• Responsible Party: Arvinas Inc.
• ClinicalTrials.gov Identifier: NCT05549505
• Other Study ID Numbers: ARV-471-BC-201; C4891025 ( Other Identifier: Pfizer )
• First Posted: September 22, 2022
• Last Update Posted: January 27, 2023
• Last Verified: January 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Arvinas Inc.:

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs