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Breast CancerPhase 1/2NCT06125522

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 C)

A Phase 1/2 study testing vepdegestrant and Samuraciclib in people with Breast Cancer, run by Pfizer at 23 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. Vepdegestrant is studied to see if it can be a possible treatment for advanced 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?
vepdegestrant and Samuraciclib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
23 sitesin 4 countries
Study dates
10 Jan 2024to 10 Sep 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

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 breast cancer. At time of enrollment this must not be amendable to surgical resection with curative intent (≥1% ER+ stained cells as per local practice on the most recent tumor biopsy HER2- tumor by IHC or in-situ hybridization per ASCO/CAP).
  • prior anticancer therapies: up to 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, 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 28 days prior to enrollment in the of 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/inducers of CYP3A, strong CYP2D6 inhibitors 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

23 sites in 4 countries.

23 sites in 4 countries

United States19 sites

  • Siteman Cancer Center - St Peters

    City of Saint Peters, Missouri, 63376

  • Siteman Cancer Center - West County

    Creve Coeur, Missouri, 63141

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • Siteman Cancer Center - North County

    Florissant, Missouri, 63031

  • UCHealth Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • UCHealth Harmony

    Fort Collins, Colorado, 80528

  • UCHealth Greeley Hospital

    Greeley, Colorado, 80634

  • UCHealth - Medical Center of the Rockies

    Loveland, Colorado, 80538

  • Clinical and Translational Research Unit (CTRU)

    Palo Alto, California, 94304

  • Stanford Cancer Institute - Clinical Trials Office

    Palo Alto, California, 94304

  • Stanford Women's Cancer Center

    Palo Alto, California, 94304

  • Highlands Oncology Group

    Rogers, Arkansas, 72758

  • Memorial Hospital East

    Shiloh, Illinois, 62269

  • Siteman Cancer Center - Shiloh

    Shiloh, Illinois, 62269

  • Highlands Oncology Group

    Springdale, Arkansas, 72762

  • 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

Other trials in United States

Italy2 sites

  • Fondazione IRCCS San Gerardo dei Tintori

    Monza, Lombardy, 20900

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

    Roma, 00168

Other trials in Italy

Belgium1 site

  • Institut Jules Bordet

    Anderlecht, Bruxelles-capitale, Région de, 1070

Other trials in Belgium

France1 site

  • Centre Georges François Leclerc

    Dijon, Côte-d'or, 21079

Other trials in France

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 AND OLDER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY C (ARV-471 IN COMBINATION WITH SAMURACICLIB)

The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat.

The study is seeking for participants who have breast cancer that:

Read more
  • is hard to treat (advanced) and may have spread to other organs (metastatic). is sensitive to hormonal therapy (it is called estrogen receptor positive).
  • is no longer responding to treatments taken before starting this study.

This study is divided into separate sub-studies.

For Sub-Study C:

All the participants will receive vepdegestrant and a medicine called samuraciclib.

Vepdegestrant and samuraciclib will be taken once in a day by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicine is safe and effective.

Participant will continue to take vepdegestrant and samuraciclib 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

C4891024 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with samuraciclib in the treatment of participants with A/MBC. The sub-study is part of Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer. 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
vepdegestrant, Samuraciclib
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.

  • vepdegestrantDrug

    Also called ARV-471 / PF-07850327

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

  • SamuraciclibDrug

    Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days

Study groups in NCT06125522
Study groupRoleWhat they receive
ARV-471 in combination with SamuraciclibExperimentalARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
Receives: Drug: vepdegestrant; Drug: Samuraciclib

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 Samuraciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).

    Measured: 28 days

  2. Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.

    Steady-state Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib

    Measured: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)

  3. Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.

    Steady-state Peak Plasma concentration ( Cmax) of ARV-471 with and without coadministration of samuraciclib

    Measured: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)

  4. 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

  5. Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.

    Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471.

    Measured: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))

  6. Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.

    Single dose Cmax of samuraciclib with and without coadministration of ARV 471.

    Measured: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))

Secondary outcomes (11)

  1. Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib

    AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to ARV-471 in combination with samuraciclib.

    Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing.

    Changes from baseline for the ECG parameters heart rate, QTcF, PR interval, and QRS complex will be summarized by treatment and time. The frequency of uncorrected QT values above 500 ms will be tabulated.

    Measured: First study drug dose through a minimum of 28 Days After Last study drug administration

  2. Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib

    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

  3. 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 1 year

  4. 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

  5. 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 1 year

  6. Phase 1b and Phase 2: Plasma concentrations of ARV-471 and samuraciclib.

    To evaluate the plasma exposure of ARV-471 and samuraciclib when ARV-471 and samuraciclib are given in combination.

    Measured: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)

  7. Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471

    AUCtau of ARV-471 with and without co-administration of samuraciclib

    Measured: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)

  8. Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471

    Cmax of ARV-471 with and without co-administration of samuraciclib

    Measured: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)

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

    To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes.

    Measured: At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment

  10. Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity

    Participants classified on basis of pathological TP53 mutation detected or not detected.

    Measured: Screening

  11. 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

Timeline

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

  1. First posted9 Nov 2023
  2. Study start10 Jan 2024
  3. Primary completion10 Sep 2026
  4. Study completion10 Sep 2026

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 samuraciclib. The decision to escalate the starting dose level 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). Phase 2 will further evaluate the preliminary antitumor activity and safety of the combination RP2D. In addition, the potential drug-drug interaction (DDI) between ARV-471 and samuraciclib will be evaluated, at the doses selected as recommended dose for expansion (RDE(s)), in a DDI Assessment Cohort(s)
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06125522
Sponsor's protocol ID
C4891024
Other IDs
2023-507125-41-00, 2023
Status last verified
Sep 2026
First submitted
16 Oct 2023
Last updated
2 Oct 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 vepdegestrant and Samuraciclib in people with Breast Cancer, run by Pfizer at 23 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: finished, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Italy, Belgium, France. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 6 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 NCT06125522.

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 Oct 2026; AzTrials last refreshed its copy on 27 Oct 2026.

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