NCT05548127

Brief Summary

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer. This study is seeking participants who have breast cancer that:

  • is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy
  • is sensitive to hormonal therapy (it is called estrogen receptor positive); and
  • is no longer responding to previous treatments This study is divided into separate sub-studies. For Sub-Study A: All participants will receive ARV-471 and a medicine called abemaciclib. ARV-471 will be given by mouth, at home, 1 time a day. Abemaciclib will be given by mouth, at home, 2 times a day. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective. Participants will continue to take ARV-471 and abemaciclib until their cancer is no longer responding, or side effects become too severe. They will have visits at the study clinic about every 4 weeks.

Trial Health

78
On Track

Trial Health Score

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

Enrollment
37

participants targeted

Target at P25-P50 for phase_1 breast-cancer

Timeline
4mo left

Started Feb 2023

Geographic Reach
4 countries

39 active sites

Status
active not recruiting

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

Study Progress91%
Feb 2023Sep 2026

First Submitted

Initial submission to the registry

August 25, 2022

Completed
27 days until next milestone

First Posted

Study publicly available on registry

September 21, 2022

Completed
5 months until next milestone

Study Start

First participant enrolled

February 23, 2023

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2026

Last Updated

February 10, 2026

Status Verified

February 1, 2026

Enrollment Period

3.5 years

First QC Date

August 25, 2022

Last Update Submit

February 5, 2026

Conditions

Keywords

TACTIVE-UUmbrella studyPROTACmetastatic breast cancer

Outcome Measures

Primary Outcomes (2)

  • Phase 1b: number of participants with dose limiting toxicities

    Dose Limiting Toxicities rate for ARV-471 in combination with abemaciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 \[28 days\]).

    28 days

  • Phase 2: percentage of participants with objective response by investigator assessment

    Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.

    Up to approximately 1 year

Secondary Outcomes (13)

  • Phase 1b and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE

    Up to 28 days after last dose of study treatment

  • Phase 1b and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters

    Up to 28 days after last dose of study treatment

  • Phase 1b and Phase 2: number of participants with lab abnormalities - chemistry parameters

    Up to 28 days after last dose of study treatment

  • Phase 1b: percentage of participants with objective response by investigator assessment

    Up to approximately 1 year

  • Phase 1b and Phase 2: duration of response by investigator assessment.

    Up to approximately 3 years

  • +8 more secondary outcomes

Study Arms (1)

ARV-471 in combination with Abemaciclib

EXPERIMENTAL

ARV-471 administered orally once daily (QD) and Abemaciclib orally twice daily (BID) on 28-day cycle

Drug: ARV-471Drug: Abemaciclib

Interventions

Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until the recommended phase 2 dose (RP2D) determined, cycles lasting 28 days

Also known as: vepdegestrant, PF-07850327
ARV-471 in combination with Abemaciclib

Daily oral dosages of Abemaciclib continuously, cycles lasting 28 days

ARV-471 in combination with Abemaciclib

Eligibility Criteria

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

You may qualify if:

  • histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy).
  • prior anticancer therapies: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (independent of the setting eg, adjuvant or advanced/metastatic)
  • at least 1 measurable lesion as defined by RECIST v1.1.
  • ECOG PS ≤1.

You may not qualify if:

  • visceral crisis at risk of life-threatening complications in the short term
  • known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
  • newly diagnosed brain metastases, or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 14 days prior to enrollment in the study.
  • history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix.
  • inflammatory breast cancer
  • impaired cardiovascular function or clinically significant cardiovascular diseases
  • concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of CYP3A and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
  • renal impairment, not adequate liver function and/or bone marrow function
  • known active infection

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (39)

Stanford Women's Cancer Center

Palo Alto, California, 94304, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

Moffitt Cancer Center - International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center

Tampa, Florida, 33612, United States

Location

Moffitt McKinley Hospital

Tampa, Florida, 33612, United States

Location

Memorial Hospital

Shiloh, Illinois, 62269, United States

Location

Siteman Cancer Center - Shiloh

Shiloh, Illinois, 62269, United States

Location

Siteman Cancer Center - WUPI

Shiloh, Illinois, 62269, United States

Location

Siteman Cancer Center - St Peters

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141, United States

Location

Siteman Cancer Center - North County

Florissant, Missouri, 63031, United States

Location

Siteman Cancer Center

St Louis, Missouri, 63108, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center - South County

St Louis, Missouri, 63129, United States

Location

U.T. MD Anderson Cancer Center, Investigational Pharmacy Services - Unit 376

Houston, Texas, 77030, United States

Location

U.T. MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Northwest Medical Specialties, PLLC

Bonney Lake, Washington, 98391, United States

Location

Northwest Medical Specialties, PLLC

Federal Way, Washington, 98003, United States

Location

Northwest Medical Specialties, PLLC

Gig Harbor, Washington, 98332, United States

Location

Northwest Medical Specialties, PLLC

Puyallup, Washington, 98373, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

BC Cancer Vancouver

Vancouver, British Columbia, V5Z 1H7, Canada

Location

BC Cancer Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

CIUSSS- saguenay-Lac-Saint-Jean

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore

Rome, Lazio, 00168, Italy

Location

Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, 10060, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], 08035, Spain

Location

Hospital Universitari Dexeus

Barcelona, Catalunya [cataluña], 08028, Spain

Location

Clinica Universidad de Navarra

Madrid, Madrid, Comunidad de, 28027, Spain

Location

Clínica Universidad de Navarra

Madrid, Madrid, Comunidad de, 28027, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, Comunidad de, 28041, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Related Links

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Phase 1b will use an escalation/de-escalation approach to determine the RP2D of ARV-471 when administered in combination with abemaciclib. The decision to de-escalate the starting dose levels of ARV 471 will be using mTPI-2 decision criteria based on the number of DLT-evaluable participants and the number of DLTs in those participants during the DLT observation period (Cycle 1 \[first 28 days\]). Phase 2 will further evaluate the preliminary antitumor activity and safety of the combination RP2D.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 25, 2022

First Posted

September 21, 2022

Study Start

February 23, 2023

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2026

Last Updated

February 10, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will share

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

More information

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