Trial Title:
A Study of ARV-471 (PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer
NCT ID:
NCT05909397
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Letrozole
Palbociclib
Conditions: Keywords:
Advanced tumor of the breast
Advanced cancer of the breast
Breast neoplasm
Breast tumor
Breast cancer
ER positive
Estrogen receptor positive
HER2-negative
Metastatic breast cancer
Palbociclib
Letrozole
ARV-471
Vepdegestrant
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ARV-471 (PF-07850327)
Description:
Pharmaceutical form: Tablets. Route of Administration: Oral
Arm group label:
Arm A (Investigational Arm)
Other name:
Vepdegestrant
Intervention type:
Combination Product
Intervention name:
Palbociclib
Description:
Pharmaceutical form: Capsules. Route of Administration: Oral.
Arm group label:
Arm A (Investigational Arm)
Other name:
IBRANCE®
Intervention type:
Drug
Intervention name:
Letrozole
Description:
Pharmaceutical form: Capsules. Route of Administration: Orally
Arm group label:
Arm B (Comparator Arm):
Other name:
FEMARA®
Intervention type:
Combination Product
Intervention name:
Palbociclib
Description:
Pharmaceutical form: Capsules. Route of Administration: Oral.
Arm group label:
Arm B (Comparator Arm):
Other name:
IBRANCE®
Summary:
The purpose of this study is to understand the safety and effects of the study medicine
ARV-471 (PF-07850327) given together with palbociclib in advanced breast cancer. In
particular, the study will compare the combination of ARV-471 plus palbociclib to
standard of care therapy (letrozole plus palbociclib). Both letrozole and palbociclib are
medicines already used for treatment of breast cancer. ARV-471 is a new medicine under
study.
This study is seeking participants who have breast cancer that:
- Have a locally advanced or metastatic disease and cannot be fully cured by surgery
or radiation therapy. A metastatic disease is when disease has spread to other parts
of the body.
- Is sensitive to hormonal therapy such as tamoxifen. This is called estrogen receptor
positive disease.
- Have not received any prior medicine for advanced disease. Example medications
include tamoxifen or letrozole or exemestane.
The study will have an open-label SLI (study lead-in) before initiation of Phase 3 trial.
During SLI, two dose levels of palbociclib in combination with ARV-471 will be explored
in parallel. Assignment to the palbociclib dose is by chance. Half of the participant
will receive one dose and the other half another palbociclib dose. The purpose of SLI is
to determine the recommended Phase 3 dose of palbociclib to be administered in
combination with ARV-471.
In the Phase 3, half of the participants will take ARV-471 plus palbociclib while the
other half will take letrozole plus palbociclib. In both SLI and Phase 3, participants
will take the study medicines by mouth, with food, once a day. Participants will take the
study medicines until breast cancer increase in size or side effects become too severe.
Side effects refer to unwanted reactions to medications. Participants will visit the
study clinic about once every 4 weeks.
Detailed description:
The purpose of this study is to demonstrate that ARV-471 in combination with palbociclib
provides superior clinical benefit compared to letrozole in combination with palbociclib
in participants with ER(+)/HER2(-) aBC who have not received any prior systemic
anti-cancer therapies for their locoregionally advanced or metastatic disease. The study
will have a Study Lead-in (SLI) and a Phase 3. In the SLI, 50 participants (approximately
25 each arm) will be randomly assigned on a 1:1 basis to one of the two dose levels
(DLs). In the randomized Phase 3, approximately 1130 eligible participants (approximately
565 each arm) will be randomized in a 1:1 ratio to the Experimental Arm (ie, ARV-471 plus
palbociclib at RP3D determined in the SLI) or Control Arm (ie, letrozole plus palbociclib
at the registered doses). Randomization will be stratified by menopausal status at study
entry, visceral disease and de novo metastatic disease.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Adult participants with loco-regional recurrent or metastatic disease not amenable
to curative treatment
- Confirmed diagnosis of ER+/HER2- breast cancer
- No prior systemic treatment for loco-regional recurrent or metastatic disease
- Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors
(RECIST) v.1.1 or non-measurable bone-only disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Phase 3 only: Participants should be willing to provide blood and tumor tissue
Exclusion Criteria:
- Disease recurrence while on, or within 12 months of completion of adjuvant endocrine
therapy
- Prior treatment with cyclin dependent kinase 4/6 inhibitors (CDK4/6i), fulvestrant,
elacestrant and other investigational drugs including novel endocrine therapies, any
selective estrogen receptor degraders (SERDs), covalent antagonists (SERCAs) and
complete ER antagonists (CERANs).
- Inadequate liver, kidney and bone marrow function
- Impaired cardiovascular function or clinically significant cardiovascular diseases
- Refractory nausea and vomiting, inability to swallow capsules and tablets whole,
chronic gastrointestinal diseases, significant gastric (total or partial) or bowel
resection that would preclude adequate absorption of study interventions.
- Current use or anticipated need for food, herbal supplements or drugs that are known
strong CYP3A4 inhibitors or inducers.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Lakeland Regional Cancer Center
Address:
City:
Lakeland
Zip:
33805
Country:
United States
Facility:
Name:
Mid Florida Hematology and Oncology Center
Address:
City:
Orange City
Zip:
32763
Country:
United States
Facility:
Name:
POM MRI & Radiology Center of Plantation
Address:
City:
Plantation
Zip:
33313
Country:
United States
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Facility:
Name:
Mercy Clinic Oncology and Hematology
Address:
City:
Ballwin
Zip:
63011
Country:
United States
Facility:
Name:
Mercy Research - David C. Pratt Cancer Center
Address:
City:
Saint Louis
Zip:
63141
Country:
United States
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
Nashville
Zip:
37203-1503
Country:
United States
Facility:
Name:
SCRI Oncology Partners
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
Virginia Oncology Associates
Address:
City:
Norfolk
Zip:
23502
Country:
United States
Facility:
Name:
Cancer Research SA
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Facility:
Name:
Cabrini Hospital -Brighton
Address:
City:
Brighton
Zip:
3186
Country:
Australia
Facility:
Name:
Barwon Health
Address:
City:
Geelong
Zip:
3220
Country:
Australia
Facility:
Name:
Cabrini Hospital - Malvern
Address:
City:
Malvern
Zip:
3144
Country:
Australia
Facility:
Name:
Hospital Santa Rita de Cassia
Address:
City:
Vitoria
Zip:
29043-260
Country:
Brazil
Facility:
Name:
Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa
Address:
City:
Porto Alegre
Zip:
90110-270
Country:
Brazil
Facility:
Name:
Centro de Pesquisa Clínica - Área Administrativa
Address:
City:
Porto Alegre
Zip:
90850-170
Country:
Brazil
Facility:
Name:
Hospital Mae de Deus
Address:
City:
Porto Alegre
Zip:
90880-480
Country:
Brazil
Facility:
Name:
A. C. Camargo Cancer Center
Address:
City:
SP
Zip:
01509-010
Country:
Brazil
Facility:
Name:
Cancer Hospital Chinese Academy of Medical Science
Address:
City:
Beijing
Zip:
100021
Country:
China
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Facility:
Name:
Hubei Cancer Hospital
Address:
City:
Wuhan
Zip:
430079
Country:
China
Facility:
Name:
The First Affiliated Hospital of Xi'an Jiaotong University
Address:
City:
Xi'an
Zip:
710061
Country:
China
Facility:
Name:
Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310016
Country:
China
Facility:
Name:
Debreceni Egyetem Klinikai Kozpont
Address:
City:
Debrecen
Zip:
04032
Country:
Hungary
Facility:
Name:
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Facility:
Name:
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Facility:
Name:
Fondazione IRCCS San Gerardo dei Tintori
Address:
City:
Monza
Zip:
20900
Country:
Italy
Facility:
Name:
Aichi Cancer Center Hospital
Address:
City:
Nagoya
Zip:
464-8681
Country:
Japan
Facility:
Name:
National Cancer Center Hospital East
Address:
City:
Kashiwa
Zip:
277-8577
Country:
Japan
Facility:
Name:
National Cancer Center Hospital
Address:
City:
Chuo-ku
Zip:
104-0045
Country:
Japan
Facility:
Name:
Nemocnica na okraji mesta n o
Address:
City:
Partizanske
Zip:
95801
Country:
Slovakia
Facility:
Name:
Fakultna nemocnica s poliklinikou J.A. Reimana Presov
Address:
City:
Presov
Zip:
080 01
Country:
Slovakia
Facility:
Name:
Institut Català d'Oncologia (ICO) - Badalona
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Facility:
Name:
Hospital Universitari Dexeus
Address:
City:
Barcelona
Zip:
08028
Country:
Spain
Facility:
Name:
Complejo Hospitalario de Jaén
Address:
City:
Jaen
Zip:
23007
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen de la Victoria
Address:
City:
Malaga
Zip:
29010
Country:
Spain
Facility:
Name:
Hospital Unviersitario Virgen Nieves
Address:
City:
Granada
Zip:
18012
Country:
Spain
Facility:
Name:
Hospital Clinico San Carlos
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Tumor Zentrum Aarau
Address:
City:
Aarau
Zip:
5000
Country:
Switzerland
Facility:
Name:
CHUV (centre hospitalier universitaire vaudois)
Address:
City:
Lausanne
Zip:
1011
Country:
Switzerland
Start date:
August 9, 2023
Completion date:
July 26, 2030
Lead sponsor:
Agency:
Pfizer
Agency class:
Industry
Collaborator:
Agency:
Arvinas Estrogen Receptor, Inc.
Agency class:
Industry
Source:
Pfizer
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05909397
https://pmiform.com/clinical-trial-info-request?StudyID=C4891002
https://www.pfizerclinicaltrials.com/nct05909397-advanced-breast-cancer-trial
