- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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)
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:
- 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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Pfizer CT.gov Call Center
- Phone Number: 1-800-718-1021
- Email: ClinicalTrials.gov_Inquiries@pfizer.com
Study Locations
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Antwerpen
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Edegem, Antwerpen, Belgium, 2650
- Not yet recruiting
- Antwerp University Hospital
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Bruxelles-capitale, Région DE
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Anderlecht, Bruxelles-capitale, Région DE, Belgium, 1070
- Not yet recruiting
- Institut Jules Bordet
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-
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Mayaguez, Puerto Rico, 00682
- Not yet recruiting
- BRCR Global - Mayagüez
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Rio Piedras, Puerto Rico, 00935
- Not yet recruiting
- Pan American Center for Oncology Trials, LLC
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Arkansas
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Fayetteville, Arkansas, United States, 72703
- Not yet recruiting
- Highlands Oncology Group
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Rogers, Arkansas, United States, 72758
- Not yet recruiting
- Highlands Oncology Group
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Springdale, Arkansas, United States, 72762
- Not yet recruiting
- Highlands Oncology Group
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Colorado
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Fort Collins, Colorado, United States, 80524
- Recruiting
- UCHealth Poudre Valley Hospital
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Fort Collins, Colorado, United States, 80528
- Recruiting
- UCHealth Harmony
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Greeley, Colorado, United States, 80634
- Recruiting
- UCHealth Greeley Hospital
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Loveland, Colorado, United States, 80538
- Recruiting
- UCHealth - Medical Center of the Rockies
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Illinois
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Shiloh, Illinois, United States, 62269
- Recruiting
- Memorial Hospital East
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Shiloh, Illinois, United States, 62269
- Recruiting
- Siteman Cancer Center - Shiloh
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Missouri
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Creve Coeur, Missouri, United States, 63141
- Recruiting
- Siteman Cancer Center - West County
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Florissant, Missouri, United States, 63031
- Recruiting
- Siteman Cancer Center - North County
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Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
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Saint Louis, Missouri, United States, 63110
- Recruiting
- Barnes-Jewish Hospital
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Saint Louis, Missouri, United States, 63129
- Recruiting
- Siteman Cancer Center - South County
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Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine - Siteman Cancer Center
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Saint Peters, Missouri, United States, 63376
- Recruiting
- Siteman Cancer Center - St Peters
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARV-471 in combination with Samuraciclib
ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
|
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
Other Names:
Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to approximately 1 year
|
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).
|
28 days
|
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
|
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
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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
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From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
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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))
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Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471.
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From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
|
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))
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Single dose Cmax of samuraciclib with and without coadministration of ARV 471.
|
From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1b and Phase 2: Duration of Response by investigator assessment.
Time Frame: Up to approximately 1 year
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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.
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Up to approximately 1 year
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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
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Up to approximately 1 year
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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.
|
Up to approximately 1 year
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Phase 2: Overall Survival
Time Frame: Through study completion, up to approximately 3 year
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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
|
Through study completion, up to approximately 3 year
|
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.
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At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
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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. |
First study drug dose through a minimum of 28 Days After Last study drug administration
|
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.
|
Up to approximately 1 year
|
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.
|
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
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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
|
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
|
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
|
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
|
Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity
Time Frame: Screening
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Participants classified on basis of pathological TP53 mutation detected or not detected.
|
Screening
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- C4891024
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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