NCT05501769

Brief Summary

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P25-P50 for phase_1 breast-cancer

Timeline
Completed

Started Sep 2022

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 9, 2022

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 15, 2022

Completed
24 days until next milestone

Study Start

First participant enrolled

September 8, 2022

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 3, 2024

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 25, 2025

Completed
Last Updated

September 26, 2025

Status Verified

September 1, 2025

Enrollment Period

1.8 years

First QC Date

August 9, 2022

Last Update Submit

September 23, 2025

Conditions

Breast Cancer

Keywords

Advanced breast cancerMetastatic breast cancerMBCEndocrine therapyEstrogen receptorER+human epidermal growth factor receptor 2HER2-ARV-471EverolimusPROTACVepdegestrant

Outcome Measures

Primary Outcomes (4)

  • Incidence of dose limiting toxicities of ARV-471 in combination with everolimus

    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

  • Recommended Phase 2 Dose (RP2D) for ARV-471 in combination with everolimus

    35 Days

  • Number of participants with adverse events as a measure of safety and tolerability of ARV-471 in combination with everolimus

    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

    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

Secondary Outcomes (6)

  • Overall response rate (ORR) in participants

    Up to approximately 1 year

  • Clinical benefit rate (CBR) in participants.

    Up to approximately 1 year

  • Duration of response (DOR) in participants

    Up to approximately 1 year

  • Maximum plasma concentrations (Cmax) of ARV-471 and everolimus

    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

    At predefined intervals throughout the treatment period, up to approximately 4 weeks after last dose of investigational products

  • +1 more secondary outcomes

Study Arms (1)

ARV-471 and Everolimus

EXPERIMENTAL

ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles

Drug: ARV-471 in combination with Everolimus

Interventions

ARV-471 in combination with EverolimusDRUG

ARV-471 oral tablets in combination with everolimus administered daily in 28 day cycles

ARV-471 and Everolimus

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Clinical Trial Site

San Diego, California, 92037, United States

Location

Clinical Trial Site

Santa Monica, California, 90404, United States

Location

Clinical Trial Site

Washington D.C., District of Columbia, 20007, United States

Location

Clinical Trial Site

Lake Mary, Florida, 32746, United States

Location

Clinical Trial Site

Ann Arbor, Michigan, 48109, United States

Location

Clinical Trial Site

Nashville, Tennessee, 37203, United States

Location

Clinical Trial Site

Barcelona, 08028, Spain

Location

Clinical Trial Site

Madrid, 28034, Spain

Location

Clinical Trial Site

Valencia, 46018, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 9, 2022

First Posted

August 15, 2022

Study Start

September 8, 2022

Primary Completion

July 3, 2024

Study Completion

August 25, 2025

Last Updated

September 26, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

ES(3)US(6)