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

Breast Cancer Clinical Trial

— VERITAC-3  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05909397
• Other study ID #: C4891002
• Secondary ID: 2022-500545-24-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 9, 2023
• Est. completion date: July 26, 2030

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1180
• Est. completion date: July 26, 2030
• Est. primary completion date: August 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• ARV-471 (PF-07850327)
Pharmaceutical form: Tablets. Route of Administration: Oral

Combination Product:
• Palbociclib
Pharmaceutical form: Capsules. Route of Administration: Oral.

Drug:
• Letrozole
Pharmaceutical form: Capsules. Route of Administration: Orally

Combination Product:
• Palbociclib
Pharmaceutical form: Capsules. Route of Administration: Oral.

Locations

Country	Name	City	State
Australia	Cancer Research SA	Adelaide	South Australia
Australia	Cabrini Hospital -Brighton	Brighton	Victoria
Australia	Barwon Health	Geelong	Victoria
Australia	Cabrini Hospital - Malvern	Malvern	Victoria
Brazil	Centro de Pesquisa Clínica - Área Administrativa	Porto Alegre	RIO Grande DO SUL
Brazil	Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa	Porto Alegre	RIO Grande DO SUL
Brazil	Hospital Mae de Deus	Porto Alegre	RIO Grande DO SUL
Brazil	A. C. Camargo Cancer Center	SP	SÃO Paulo
Brazil	Hospital Santa Rita de Cassia	Vitoria	Espírito Santo
China	Cancer Hospital Chinese Academy of Medical Science	Beijing	Beijing
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Italy	IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"	Meldola	Emilia-romagna
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli	Campania
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Slovakia	Nemocnica na okraji mesta n o	Partizanske
Slovakia	Fakultna nemocnica s poliklinikou J.A. Reimana Presov	Presov
Spain	Institut Català d'Oncologia (ICO) - Badalona	Badalona	Barcelona [barcelona]
Spain	Hospital Universitari Dexeus	Barcelona	Catalunya [cataluña]
Spain	Hospital Unviersitario Virgen Nieves	Granada
Spain	Complejo Hospitalario de Jaén	Jaen	Jaén
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga	Málaga
Switzerland	Tumor Zentrum Aarau	Aarau	Aargau
Switzerland	CHUV (centre hospitalier universitaire vaudois)	Lausanne	Vaud
United States	University of Michigan	Ann Arbor	Michigan
United States	Mercy Clinic Oncology and Hematology	Ballwin	Missouri
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	Mercy Research - David C. Pratt Cancer Center	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Arvinas Estrogen Receptor, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  China,  Hungary,  Italy,  Japan,  Slovakia,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study Lead-in (SLI): Incidence of Grade 4 neutropenia	It is defined as the number of participants with Grade 4 neutropenia AE (graded by NCI CTCAE v.5.0) with onset within the first 4 cycles divided by the number of participants.	From randomization date up to Cycle 4 (each cycle is 28 days).
Primary	SLI: Incidence of dose reduction	It is defined as the number of participants reducing the dose of palbociclib and/or ARV-471 due to any cause occurring within the first 4 cycles divided by the number of participants.	From randomization date up to Cycle 4 (each cycle is 28 days).
Primary	SLI: Incidence of drug discontinuation.	It is defined as the number of participants discontinuing palbociclib and/or ARV-471 due to any cause occurring within the first 4 cycles divided by the number of participants.	From randomization date up to Cycle 4 (each cycle is 28 days).
Primary	Phase 3: Progression-Free Survival	Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by Blinded Independent Central Review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or death due to any cause, whichever come first.	From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.
Secondary	SLI and Phase 3. Objective Response Rate	Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as best overall response determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1, from the date of randomization to the date of disease progression or death due to any cause, whichever occurs first.	From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).
Secondary	SLI and Phase 3: Duration of Response	Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1 or death due to any cause, whichever occurs first.	From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).
Secondary	SLI and Phase 3: Clinical Benefit Rate	Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR at any time or SD or non CR/non PD for at least 24 weeks determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1, from the date of randomization until disease progression or death due to any cause, whichever occurs first.	Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).
Secondary	Phase 3: Overall Survival	Overall survival is defined as the time interval from the date of randomization to the date of documented death, due to any cause.	From randomization date, every 3 months, to date of death (up to approximately 6 years)
Secondary	SLI and Phase 3: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	It is defined as the number of participants with TEAEs and SAEs divided by the number of participants. AEs and SAEs will be graded according to NCI CTCAE V5.0.	From baseline to date to end of treatment (up to approximately 4 years)
Secondary	SLI and Phase 3: Incidence of laboratory abnormalities	It is defined as the number of participants with laboratory abnormalities divided by the number of participants. Laboratory abnormalities will be graded according to NCI CTCAE V5.0.	From baseline to end of treatment (up to approximately 4 years)
Secondary	SLI and Phase 3: Incidence of Electrocardiogram (ECG) Abnormalities	It is defined as the number of participants with ECG abnormalities divided by the number of participants. ECG abnormalities will be graded according to NCI CTCAE V5.0.	From baseline up to the end of treatment (up to approximately 4 years)
Secondary	SLI and Phase 3: Plasma concentrations of ARV-471 and palbociclib	Plasma concentrations of ARV-471 and palbociclib	From randomization date up to Cycle 5 (each cycle is 28 days)
Secondary	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)	Change from baseline between treatment comparison in Quality of Life using the EQ-5D 5L questionnaire.	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
Secondary	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)	Change from baseline between treatment comparison in Quality of Life using the EORTC QLQ-C30 questionnaire.	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.
Secondary	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.	Change from baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) questionnaire.	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.
Secondary	Phase 3: Changes from baseline in plasma ctDNA (Circulating Deoxyribonucleic Acid)	Quantitative changes from baseline	From baseline to end of treatment (up to approximately 4 years)

External Links

•   To obtain contact information for a study center near you, click here.
•   VERITAC-3 Study on Pfizer Clinical Trials