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Breast CancerPhase 1/2NCT05548127

TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study A)

A Phase 1/2 study testing ARV-471 and Abemaciclib in people with Breast Cancer, run by Pfizer at 37 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
ARV-471 and Abemaciclib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
37 sitesin 4 countries
Study dates
23 Feb 2023to 24 Mar 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

37 sites in 4 countries.

37 sites in 4 countries

United States23 sites

  • Northwest Medical Specialties, PLLC

    Bonney Lake, Washington, 98391

  • Siteman Cancer Center - St Peters

    City of Saint Peters, Missouri, 63376

  • Siteman Cancer Center - West County

    Creve Coeur, Missouri, 63141

  • Northwest Medical Specialties, PLLC

    Federal Way, Washington, 98003

  • Siteman Cancer Center - North County

    Florissant, Missouri, 63031

  • Northwest Medical Specialties, PLLC

    Gig Harbor, Washington, 98332

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

    Houston, Texas, 77030

  • U.T. MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Stanford Women's Cancer Center

    Palo Alto, California, 94304

  • Northwest Medical Specialties, PLLC

    Puyallup, Washington, 98373

  • UCSF Medical Center at Mission Bay

    San Francisco, California, 94158

  • Memorial Hospital

    Shiloh, Illinois, 62269

  • Siteman Cancer Center - Shiloh

    Shiloh, Illinois, 62269

  • Siteman Cancer Center

    St Louis, Missouri, 63108

  • Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Washington University School of Medicine - Siteman Cancer Center

    St Louis, Missouri, 63110

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center - South County

    St Louis, Missouri, 63129

  • Northwest Medical Specialties, PLLC

    Tacoma, Washington, 98405

  • Moffitt Cancer Center - International Plaza

    Tampa, Florida, 33607

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

    Tampa, Florida, 33612

  • Moffitt McKinley Hospital

    Tampa, Florida, 33612

Other trials in United States

Canada6 sites

  • CIUSSS- saguenay-Lac-Saint-Jean

    Chicoutimi, Quebec, G7H 5H6

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • The Ottawa Hospital - General Campus

    Ottawa, Ontario, K1H 8L6

  • Sunnybrook Research Institute

    Toronto, Ontario, M4N 3M5

  • BC Cancer Vancouver

    Vancouver, British Columbia, V5Z 1H7

  • BC Cancer Vancouver

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Spain6 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, Barcelona [barcelona], 08035

  • Hospital Universitari Dexeus

    Barcelona, Catalunya [cataluña], 08028

  • Clinica Universidad de Navarra

    Madrid, Madrid, Comunidad de, 28027

  • Hospital Universitario 12 de Octubre

    Madrid, Madrid, Comunidad de, 28041

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Virgen Del Rocio

    Seville, 41013

Other trials in Spain

Italy2 sites

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

    Candiolo, Torino, 10060

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

    Rome, Lazio, 00168

Other trials in Italy

About this study

Official title: TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 YEARS AND OVER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY A (ARV-471 IN COMBINATION WITH ABEMACICLIB)

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:

Read more
  • 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.

Read the detailed description

C4891006 is a sub-study from the Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with Estrogen Receptor Positive (ER+) Advanced or Metastatic Breast Cancer (A/MBC). ARV-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in ER+ breast cancer.

Conditions
Breast Cancer
Being tested
ARV-471, Abemaciclib
Keywords
TACTIVE-U, Umbrella study, PROTAC, metastatic breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARV-471Drug

    Also called vepdegestrant, PF-07850327

    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

  • AbemaciclibDrug

    Daily oral dosages of Abemaciclib continuously, cycles lasting 28 days

Study groups in NCT05548127
Study groupRoleWhat they receive
ARV-471 in combination with AbemaciclibExperimentalARV-471 administered orally once daily (QD) and Abemaciclib orally twice daily (BID) on 28-day cycle
Receives: Drug: ARV-471; Drug: Abemaciclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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]).

    Measured: 28 days

  2. 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.

    Measured: Up to approximately 1 year

Secondary outcomes (13)

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

    An adverse event (AE) were any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug.

    AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and coded using MedDRA were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death.

    Measured: Up to 28 days after last dose of study treatment

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

    Blood samples were collected for the analysis of following hematology and coagulation parameters: hemoglobin [g/L], platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils [10^9/L]; partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time. Number of participants with hematological and coagulation abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death.

    For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.

    Measured: Up to 28 days after last dose of study treatment

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

    Blood samples were collected for analysis of clinical chemistry parameters. These included: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, [international unit per liter (IU/L)] ; Lipase and amilase [IU/L] (limited to cycle1 only); Albumin, bilirubin, urea ,calcium, creatinine, glucose, magnesium, phosphate, uric acid, chloride, potassium and sodium [millimol per liter (mmol/L)]; eGFR [milliliter per minute (ml/min)]. Number of participants with blood chemistry abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death.

    For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.

    Measured: Up to 28 days after last dose of study treatment

  4. Phase 1b: 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.

    Measured: Up to approximately 1 year

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

    Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

    Measured: Up to approximately 3 years

  6. Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.

    Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) ≥24 weeks

    Measured: Up to approximately 1 year

  7. Phase 1b and Phase 2: Progression Free Survival by investigator assessment.

    Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs first.

    Measured: Up to approximately 3 years

  8. Phase 2: Overall Survival

    Overall Survival (OS) is defined as the time from the date of first dose of study interventions to the date of death due to any cause

    Measured: Through study completion, up to approximately 3 year

  9. Phase 2:ctDNA plasma quantitative changes from pre-treatment

    To assess changes from baseline levels in plasma circulating DNA (ctDNA) with treatment and to evaluate potential predictability of their associations with clinical outcome

    Measured: Day 1, 29 and 57 and End of Treatment (an average of 1 year)

  10. Phase 1b: Area Under the Curve from Time Zero to end of dosing interval Evaluation of abemaciclib with or without ARV-471

    Exposure (AUCtau) of abemaciclib with and without co-administration of ARV-471

    Measured: Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43

  11. Phase 1b: Maximum Observed Plasma Concentration (Cmax) of abemaciclib with or without ARV-471

    Concentration (Cmax) of abemaciclib with and without co-administration of ARV-471

    Measured: Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43

  12. Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471

    Plasma concentration of ARV-471

    Measured: Phase 1b: pre-dose Day 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day 15; post dose Day 29 and 43. Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169

  13. Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of abemaciclib

    Plasma concentration of abemaciclib

    Measured: Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29, 43 and 57 Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2022
  2. Study start23 Feb 2023
  3. Primary completion24 Mar 2027 (estimated)
  4. Study completion24 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05548127
Sponsor's protocol ID
C4891006
Other IDs
2022-502228-34-00
Status last verified
Aug 2026
First submitted
25 Aug 2022
Last updated
2 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ARV-471 and Abemaciclib in people with Breast Cancer, run by Pfizer at 37 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Canada, Spain, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: number of participants with dose limiting toxicities (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05548127.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.

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