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)
vepdegestrant: Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
Samuraciclib: Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
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).
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 Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib
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
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.
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 AUC0-72 of samuraciclib with and without coadministration of ARV 471.
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.
Trial sites (21)
Facility
City
Region
Status
Highlands Oncology Group
Fayetteville
Arkansas
Highlands Oncology Group
Rogers
Arkansas
Highlands Oncology Group
Springdale
Arkansas
Clinical and Translational Research Unit (CTRU)
Palo Alto
California
Stanford Women's Cancer Center
Palo Alto
California
UCHealth Poudre Valley Hospital
Fort Collins
Colorado
UCHealth Harmony
Fort Collins
Colorado
UCHealth Greeley Hospital
Greeley
Colorado
UCHealth - Medical Center of the Rockies
Loveland
Colorado
Memorial Hospital East
Shiloh
Illinois
Siteman Cancer Center - Shiloh
Shiloh
Illinois
Siteman Cancer Center - St Peters
City of Saint Peters
Missouri
Siteman Cancer Center - West County
Creve Coeur
Missouri
Siteman Cancer Center - North County
Florissant
Missouri
Barnes-Jewish Hospital
St Louis
Missouri
Washington University School of Medicine - Siteman Cancer Center
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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