ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer (TACTIVE-E)

September 23, 2025 updated by: Arvinas Estrogen Receptor, Inc.

A Phase 1b Trial of ARV-471 in Combination With Everolimus in Patients With ER+, HER2- Advanced or Metastatic Breast Cancer

A phase 1b study to assess the combination of ARV-471 and everolimus in participants with advanced or metastatic ER+/HER2- breast cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1b study to assess the safety and tolerability of ARV-471 in combination with everolimus in participants with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer, who have received a prior CDK4/6 inhibitor and endocrine therapy in the advanced/metastatic setting.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08028
        • Clinical Trial Site
      • Madrid, Spain, 28034
        • Clinical Trial Site
      • Valencia, Spain, 46018
        • Clinical Trial Site
  • United States
    • California
      • San Diego, California, United States, 92037
        • Clinical Trial Site
      • Santa Monica, California, United States, 90404
        • Clinical Trial Site
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Clinical Trial Site
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Clinical Trial Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Clinical Trial Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed ER+ and HER2-advanced breast cancer (metastatic, recurrent, or unresectable)
  • Women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression
  • Measurable disease or non-measurable (evaluable) disease per RECIST v1.1
  • Received a minimum of 1 and up to 3 lines of anti-cancer therapy in the advanced/metastatic setting: must have received and progressed on (or were intolerant to) a CDK 4/6 inhibitor, either alone or in combination; must have received at least one endocrine therapy, either alone or in combination; may have received up to one line of chemotherapy
  • Must be willing to use dexamethasone mouthwash for the prevention of everolimus-induced stomatitis
  • ECOG performance status of 0 or 1

Exclusion Criteria:

  • Untreated brain metastases or brain metastases requiring steroids above physiologic replacement doses
  • Prior treatment with ARV-471
  • Prior treatment targeting mTOR (e.g. everolimus)
  • Prior anticancer or investigational drug treatment within 28 days (fulvestrant) or 14 days (tamoxifen or aromatase inhibitor, or CDK 4/6 inhibitor) before the first dose of study drug
  • Prior anticancer or investigational anticancer drug therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of study drug, except as mentioned above
  • Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, 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, ongoing cardiac arrythmias/dysrhythmias, atrial fibrillation
  • Hypertension that cannot be controlled by medication (>150/90 mmHg despite optimal medical therapy)
  • Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
  • Known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung function
  • Live vaccines within 14 days before the first dose of study drug
  • Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug
  • Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to more than 25% of the bone marrow

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ARV-471 and Everolimus
ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles
Drug: ARV-471 in combination with Everolimus
ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose limiting toxicities of ARV-471 in combination with everolimus
Time Frame: 35 Days
Dose limiting toxicities in the first 35 days of the study combination treatment characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study drug
35 Days
Number of participants with adverse events as a measure of safety and tolerability of ARV-471 in combination with everolimus
Time Frame: 28 calendar days after participant discontinues study treatment
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination
28 calendar days after participant discontinues study treatment
Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471 in combination with everolimus
Time Frame: 28 calendar days after participant discontinues study treatment
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing
28 calendar days after participant discontinues study treatment
Recommended Phase 2 Dose (RP2D) for ARV-471 in combination with everolimus
Time Frame: 35 Days
35 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR) in participants
Time Frame: Up to approximately 1 year
Up to approximately 1 year
Duration of response (DOR) in participants
Time Frame: Up to approximately 1 year
Up to approximately 1 year
Maximum plasma concentrations (Cmax) of ARV-471 and everolimus
Time Frame: At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
Time to maximum plasma concentrations (Tmax) of ARV-471 and everolimus
Time Frame: At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
Area under the concentration-time curve over 24 hours at steady state (AUC(0-24)) of ARV-471 and everolimus
Time Frame: At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products
Clinical benefit rate (CBR) in participants.
Time Frame: Up to approximately 1 year
Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer.
Up to approximately 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arvinas Estrogen Receptor, Inc.

Collaborators

Pfizer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 8, 2022

Primary Completion (Actual)

July 3, 2024

Study Completion (Actual)

August 25, 2025

Study Registration Dates

First Submitted

August 9, 2022

First Submitted That Met QC Criteria

August 12, 2022

First Posted (Actual)

August 15, 2022

Study Record Updates

Last Update Posted (Estimated)

September 26, 2025

Last Update Submitted That Met QC Criteria

September 23, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARV-471-mBC-102
  • C4891020 (Other Identifier: Pfizer)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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