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NCT Number: NCT06125522

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)

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:

* 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Institut Jules Bordet, Anderlecht, Bruxelles-capitale, Région de, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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
  • 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

Treatment and study plan

vepdegestrant

Drug

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

Other names: ARV-471 / PF-07850327

Samuraciclib

Drug

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

Primary outcomes

  1. Phase 1b: Number of Participants With Dose Limiting Toxicities

    Time frame: 28 days

    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).

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

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

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

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

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

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

  4. Phase 2: Percentage of Participants With Objective Response by investigator assessment

    Time frame: Up to approximately 1 year

    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.

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

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

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

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

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

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

Secondary outcomes

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

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

    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.

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

    Time frame: Up to approximately 1 year

    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.

  3. Phase 1b and Phase 2: Duration of Response by investigator assessment.

    Time frame: Up to approximately 1 year

    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.

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

    Time frame: Up to approximately 1 year

    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

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

    Time frame: Up to approximately 1 year

    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.

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

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

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

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

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

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

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

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

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

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

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

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

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

    Time frame: Screening

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

  11. Phase 2: Overall Survival

    Time frame: Through study completion, up to approximately 3 year

    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

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Collaborators

  • Arvinas Estrogen Receptor, Inc.
  • Carrick Therapeutics Limited

Registry information

Official study 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)

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Nov 9, 2023
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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