A Phase 1/2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT04072952

Last Updated: 2026-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

217 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-05

Study Completion Date

2026-02-27

Brief Summary

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This is a Phase 1/2 dose escalation and cohort expansion study and will assess the safety, tolerability and anti-tumor activity of ARV-471 alone and in combination with palbociclib (IBRANCE®) in patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) locally advanced or metastatic breast cancer, who have received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Subsequent dose level is determined by the Cohort Review Committee after the initial starting dose cohort and each subsequent dose cohort completes the first 28 days of treatment

Dose escalation followed by expansion at a Recommended Phase 2 Dose (RP2D) including a combination cohort with palbociclib (IBRANCE®)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ARV-471

Parts A and B: ARV-471 administered once daily (QD) or twice daily (BID) for 28 day cycles.

Group Type EXPERIMENTAL

ARV-471

Intervention Type DRUG

Parts A and B: ARV-471 administered QD or BID for 28 day cycles.

ARV-471 and palbociclib (IBRANCE®)

Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days.

Group Type EXPERIMENTAL

ARV-471 in combination with palbociclib (IBRANCE®)

Intervention Type DRUG

Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days

Interventions

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ARV-471

Parts A and B: ARV-471 administered QD or BID for 28 day cycles.

Intervention Type DRUG

ARV-471 in combination with palbociclib (IBRANCE®)

Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Part A, Part B, and Part C:

* Patients at least 18 years of age at the time of signing the informed consent.
* Patients must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer for which standard curative therapy is no longer effective or does not exist.
* Patients must have measurable or non-measurable disease by RECIST criteria (version1.1), with radiologic tumor assessments performed within 28 days of the first dose of therapy.
* Patients must be willing to undergo a core biopsy of accessible tumor within 4 weeks prior to the initiation of study treatment and a follow-up biopsy on treatment for ER immunohistochemistry (IHC) testing and pharmacodynamics (PD) studies. (Patients without accessible tumor tissue may be eligible after discussion with the Medical Monitor.)
* Women must be postmenopausal due to surgical or natural menopause.

Part A:

\- Patients must have received at least 2 prior endocrine regimens in any setting (neoadjuvant, adjuvant or advanced/metastatic) a CDK4/6 inhibitor and up to 3 prior regimens of cytotoxic chemotherapy in the locally advanced or metastatic setting.

Part B:

* Patients must have received at least 1 prior endocrine regimen for a minimum of 6 months in the locally advanced or metastatic setting; if more than 1 prior endocrine regimen has been administered, only one of the regimens must have been administered for a minimum of 6 months in the locally advanced or metastatic setting
* Patients must have received a CDK4/6 inhibitor
* Patients must have received up to 1 prior regimen of cytotoxic chemotherapy in the locally advanced or metastatic setting
* Women must be postmenopausal due to surgical or natural menopause.

Part C:

* Patients must have received at least one prior endocrine regimen.
* Patients must have received no more than two prior chemotherapy regimens for advanced disease.
* Women must be postmenopausal due to surgical or natural menopause.

Exclusion Criteria

Part A, Part B, and Part C:

* Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses). Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to first dose of study drug, have discontinued high-dose corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable as judged by the Investigator.
* Receipt of prior anti-cancer or other investigational therapy within 14 days prior to the first administration of study drug.
* Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to \>25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Arvinas Estrogen Receptor, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Clinical Trial Site

Palo Alto, California, United States

Site Status

Clinical Trial Site

San Francisco, California, United States

Site Status

Clinical Trial Site

Santa Monica, California, United States

Site Status

Clinical Trial Site

Norwalk, Connecticut, United States

Site Status

Clinical Trial Site

Fort Myers, Florida, United States

Site Status

Clinical Trial Site

Tampa, Florida, United States

Site Status

Clinical Trial Site

Chicago, Illinois, United States

Site Status

Clinical Trial Site

Boston, Massachusetts, United States

Site Status

Clinical Trial Site

Boston, Massachusetts, United States

Site Status

Clinical Trial Site

Ann Arbor, Michigan, United States

Site Status

Clinical Trial Site

St Louis, Missouri, United States

Site Status

Clinical Trial Site

East Brunswick, New Jersey, United States

Site Status

Clinical Trial Site

The Bronx, New York, United States

Site Status

Clinical Trial Site

Charlotte, North Carolina, United States

Site Status

Clinical Trial Site

Nashville, Tennessee, United States

Site Status

Clinical Trial Site

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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C4891019

Identifier Type: OTHER

Identifier Source: secondary_id

ARV-471-mBC-101

Identifier Type: -

Identifier Source: org_study_id

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