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.
Clinical Trial Details
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Breast Cancer
Vepdegestrant (ARV-471)*
Vepdegestrant is an investigational compound. Its safety and efficacy have not been established. * Vepdegestrant is being co-developed with Arvinas.
Palbociclib
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)
Phase 3
NCT05909397
Active enrolling
Locations
United States, Australia, Brazil, China, Hungary, Italy, Japan, Slovakia, Spain, Switzerland
Study design
Participant Group/Arm
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
Intervention/Treatment
DRUG: ARV-471 (PF-07850327)
Pharmaceutical form: Tablets. Route of Administration: Oral
Participant Group/Arm
ACTIVE_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.
Intervention/Treatment
DRUG: Letrozole
Pharmaceutical form: Capsules. Route of Administration: Orally
Key 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.
Key dates
Study start date
- August 2023
Estimated primary completion date
- July 2030
Key endpoints
Primary Outcome Measures
Outcome Measure
Study Lead-in (SLI): Incidence of Grade 4 neutropenia
Measure Description
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.
Time Frame
From randomization date up to Cycle 4 (each cycle is 28 days).
Outcome Measure
SLI: Incidence of dose reduction
Measure Description
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.
Time Frame
From randomization date up to Cycle 4 (each cycle is 28 days).
Outcome Measure
SLI: Incidence of drug discontinuation.
Measure Description
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.
Time Frame
From randomization date up to Cycle 4 (each cycle is 28 days).
Outcome Measure
Phase 3: Progression-Free Survival
Measure Description
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.
Time Frame
From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.
Secondary Outcome Measures:
Outcome Measure
SLI and Phase 3. Objective Response Rate
Measure Description
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.
Time Frame
From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).
Outcome Measure
SLI and Phase 3: Duration of Response
Measure Description
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.
Time Frame
From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).
Outcome Measure
SLI and Phase 3: Clinical Benefit Rate
Measure Description
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.
Time Frame
Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).
Outcome Measure
Phase 3: Overall Survival
Measure Description
Overall survival is defined as the time interval from the date of randomization to the date of documented death, due to any cause.
Time Frame
From randomization date, every 3 months, to date of death (up to approximately 6 years)
Outcome Measure
SLI and Phase 3: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measure Description
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.
Time Frame
From baseline to date to end of treatment (up to approximately 4 years)
Outcome Measure
SLI and Phase 3: Incidence of laboratory abnormalities
Measure Description
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.
Time Frame
From baseline to end of treatment (up to approximately 4 years)
Outcome Measure
SLI and Phase 3: Incidence of Electrocardiogram (ECG) Abnormalities
Measure Description
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.
Time Frame
From baseline up to the end of treatment (up to approximately 4 years)
Outcome Measure
SLI and Phase 3: Plasma concentrations of ARV-471 and palbociclib
Measure Description
Plasma concentrations of ARV-471 and palbociclib
Time Frame
From randomization date up to Cycle 5 (each cycle is 28 days)
Outcome 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)
Measure Description
Change from baseline between treatment comparison in Quality of Life using the EQ-5D 5L questionnaire.
Time Frame
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
Outcome 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)
Measure Description
Change from baseline between treatment comparison in Quality of Life using the EORTC QLQ-C30 questionnaire.
Time Frame
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.
Outcome 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.
Measure Description
Change from baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) questionnaire.
Time Frame
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.
Outcome Measure
Phase 3: Changes from baseline in plasma ctDNA (Circulating Deoxyribonucleic Acid)
Measure Description
Quantitative changes from baseline
Time Frame
From baseline to end of treatment (up to approximately 4 years)
Number of participants
1180
Collaborators and investigators
Sponsor: Pfizer
Collaborator: Arvinas Estrogen Receptor, Inc.