The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Vepdegestrant is an investigational compound. Its safety and efficacy have not been established. * Vepdegestrant is being co-developed with Arvinas.
Active Not-enrolling
United States, Australia, Brazil, China, Hungary, Italy, Japan, Slovakia, Spain, Switzerland
EXPERIMENTAL: Arm A (Investigational Arm)
Participants will receive: * ARV-471, orally, once daily, continuously, in a 28-day cycle, plus * Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment in a 28 day cycle
DRUG: ARV-471 (PF-07850327)
Pharmaceutical form: Tablets. Route of Administration: OralACTIVE_COMPARATOR: Arm B (Comparator Arm):
Participants will receive: * Letrozole, orally, once daily, continuously, in a 28-day cycle, plus * Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment, in a 28-day cycle.
DRUG: Letrozole
Pharmaceutical form: Capsules. Route of Administration: OrallyStudy 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).
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).
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).
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.
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).
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).
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).
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)
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)
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)
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)
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)
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
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.
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.
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)
1180
Sponsor: Pfizer
Collaborator: Arvinas Estrogen Receptor, Inc.
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT05909397
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