Clinical trial NCT05909397: A Study of Vepdegestrant (ARV-471, PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer
Official title: A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY OF ARV-471(PF-07850327) PLUS PALBOCICLIB VERSUS LETROZOLE PLUS PALBOCICLIB FOR THE TREATMENT OF PARTICIPANTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI-CANCER TREATMENT FOR ADVANCED DISEASE (VERITAC-3)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Arvinas Estrogen Receptor, Inc.
First posted: 2023-06-18
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Study Lead-in (SLI): Incidence of Grade 4 neutropenia
timeFrame: From randomization date up to Cycle 4 (each cycle is 28 days).
measure: SLI: Incidence of dose reduction
timeFrame: From randomization date up to Cycle 4 (each cycle is 28 days).
measure: SLI: Incidence of drug discontinuation.
timeFrame: From randomization date up to Cycle 4 (each cycle is 28 days).
measure: Phase 3: Progression-Free Survival
timeFrame: From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.
Secondary outcomes:
measure: SLI and Phase 3. Objective Response Rate
timeFrame: From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).
measure: SLI and Phase 3: Duration of Response
timeFrame: From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).
measure: SLI and Phase 3: Clinical Benefit Rate
timeFrame: Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).
measure: Phase 3: Overall Survival
timeFrame: From randomization date, every 3 months, to date of death (up to approximately 6 years)
measure: SLI and Phase 3: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From baseline to date to end of treatment (up to approximately 4 years)
measure: SLI and Phase 3: Incidence of laboratory abnormalities
timeFrame: From baseline to end of treatment (up to approximately 4 years)
measure: SLI and Phase 3: Incidence of Electrocardiogram (ECG) Abnormalities
timeFrame: From baseline up to the end of treatment (up to approximately 4 years)
measure: SLI and Phase 3: Plasma concentrations of ARV-471 and palbociclib
timeFrame: From randomization date up to Cycle 5 (each cycle is 28 days)
measure: Phase 3: Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
timeFrame: From baseline, each cycle up to cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days
measure: Phase 3: Disease-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)
timeFrame: From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.
measure: Phase 3: Disease- and treatment-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) breast cancer module (QLQ-BR23) questionnaire.
timeFrame: From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.
measure: Phase 3: Changes from baseline in plasma ctDNA (Circulating Deoxyribonucleic Acid)
timeFrame: From baseline to end of treatment (up to approximately 4 years)
Other outcomes:
Locations:
city: Plantation
country: United States
facility: BRCR Medical Center Inc
state: Florida
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Adelaide
country: Australia
facility: Cancer Research SA
state: South Australia
city: Geelong
country: Australia
facility: Barwon Health
state: Victoria
city: Vitoria
country: Brazil
facility: Hospital Santa Rita de Cassia
state: Espírito Santo
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa Clínica - Área Administrativa
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus
state: RIO Grande DO SUL
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
state: Campania
city: Meldola
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
state: Emilia-romagna
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Lombardia
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Partizanske
country: Slovakia
facility: Nemocnica na okraji mesta n o
city: Presov
country: Slovakia
facility: Fakultna nemocnica s poliklinikou J.A. Reimana Presov
city: Badalona
country: Spain
facility: Institut Català d'Oncologia (ICO) - Badalona
state: Barcelona [barcelona]
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus
state: Catalunya [cataluña]
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaén
state: Jaén
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
state: Málaga
city: Granada
country: Spain
facility: Hospital Unviersitario Virgen Nieves
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Aarau
country: Switzerland
facility: Tumor Zentrum Aarau
state: Aargau
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: