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 B)
ARV-471: Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
Ribociclib: Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days
Study summary
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer.
This study is seeking participants who have breast cancer that:
* is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy
* is sensitive to hormonal therapy (it is called estrogen receptor positive); and
* is no longer responding to previous treatments
This study is divided into separate sub-studies.
For Sub-Study B:
All participants will receive ARV-471 and a medicine called ribociclib. ARV-471 and ribociclib will be given at the same time by mouth, at home, 1 time a day.
The experiences of people receiving the study medicine will be examined. This will help determine if the study medicine is safe and effective.
Participants will continue to take ARV-471 and ribociclib 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 ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy).
* prior anticancer therapies: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1, and only 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 14 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 and strong/moderate inducers of CYP3A 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 — Cycle 1 (28 days) Dose Limiting Toxicities rate for ARV-471 in combination with Ribociclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 \[28 days\]).
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 cohort: Area Under the Curve from Time Zero to end of dosing interval Evaluation of ribociclib with and without co-administration of ARV-471 — pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Exposure (AUCtau) of ribociclib with and without co-administration of ARV-471
Drug Drug Interaction cohort: Maximum Plasma Concentration (Cmax) of ribociclib with and without co-administration of ARV-471 — pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
Trial sites (29)
Facility
City
Region
Status
Stanford Women's Cancer Center
Palo Alto
California
UCSF Medical Center at Mission Bay
San Francisco
California
Moffitt Cancer Center - International Plaza
Tampa
Florida
Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
Tampa
Florida
Moffitt Cancer Center
Tampa
Florida
Moffitt McKinley Hospital
Tampa
Florida
Siteman Cancer Center - WUPI
Shiloh
Illinois
Brigham and Women's Hospital
Boston
Massachusetts
Dana-Farber Cancer Institute
Boston
Massachusetts
Dana-Farber Cancer Institute - Chestnut Hill
Newton
Massachusetts
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
Siteman Cancer Center
St Louis
Missouri
Barnes Jewish Hospital Department of Laboratories
St Louis
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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