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)
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT06125522
- Lead Sponsor
- Pfizer
- Brief 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. 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 11
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ARV-471 in combination with Samuraciclib vepdegestrant ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles ARV-471 in combination with Samuraciclib Samuraciclib ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
- Primary Outcome Measures
Name Time Method Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471. 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
Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib. 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.
Phase 1b: Number of Participants With Dose Limiting Toxicities 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).
Phase 2: Percentage of Participants With Objective Response by investigator assessment 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.
- Secondary Outcome Measures
Name Time Method Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471 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
Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity Screening Participants classified on basis of pathological TP53 mutation detected or not detected.
Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib 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.Phase 1b and Phase 2: Plasma concentrations of ARV-471 and samuraciclib. 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.
Phase 2: Overall Survival 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
Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib 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.
Phase 1b and Phase 2: Duration of Response by investigator assessment. 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.
Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment. 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
Phase 2:ctDNA plasma quantitative changes from pre-treatment 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.
Phase 1b and Phase 2: Progression Free Survival by investigator assessment. 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.
Trial Locations
- Locations (19)
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
UCHealth Poudre Valley Hospital
🇺🇸Fort Collins, Colorado, United States
UCHealth Harmony
🇺🇸Fort Collins, Colorado, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Stanford Cancer Institute - Clinical Trials Office
🇺🇸Palo Alto, California, United States
UCHealth Greeley Hospital
🇺🇸Greeley, Colorado, United States
UCHealth - Medical Center of the Rockies
🇺🇸Loveland, Colorado, United States
Memorial Hospital East
🇺🇸Shiloh, Illinois, United States
Siteman Cancer Center - Shiloh
🇺🇸Shiloh, Illinois, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Siteman Cancer Center - North County
🇺🇸Florissant, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - St Peters
🇺🇸Saint Peters, Missouri, United States
Institut Jules Bordet
🇧🇪Anderlecht, Bruxelles-capitale, Région DE, Belgium
Centre Georges François Leclerc
🇫🇷Dijon, Côte-d'or, France
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Lombardia, Italy