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Breast NeoplasmsPhase 1NCT05463952

A Study to Learn About the Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (BC)

A Phase 1 study testing vepdegestrant in people with Breast Neoplasms, run by Pfizer at 3 sites in Japan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this clinical trial is to learn about the safety, tolerability, Pharmacokinetics (PK), and preliminary efficacy of ARV-471 as monotherapy in Japanese participants with ER+/HER2- locally advanced or metastatic breast cancer (mBC). Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Breast Neoplasms
What is being tested?
vepdegestrant
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
3 sitesJapan
Study dates
16 Aug 2022to 31 Mar 2025
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants (women and men) at least 20 years of age at the time of signing the informed consent.
  • Histological or cytological diagnosis of ER+/HER2- advanced breast cancer that is metastatic, recurrent, or locally advanced unresectable breast cancer.
  • Participants who are resistant to standard therapy or for which no standard therapy is available or have received.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Infromed Consent Document (ICD) and in this protocol.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
  • Adequate Bone Marrow or Coagulation Function.
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  • Adequate Renal Function, defined as an estimated creatinine clearance ≥60 mL/min as calculated using the method standard for the institution.
  • Adequate Liver Function.
  • Participants with brain metastases must meet all the specified conditions.
  • Resolution of acute effects of any prior therapy to either baseline severity or CTCAE version 5.0 Grade ≤1.

Who cannot join

  • Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease.
  • Participants sustaining major surgery defined as a complex procedure performed under regional or general anesthesia with a recovery period of at least 4 weeks prior to study enrollment.
  • Known or suspected hypersensitivity or severe allergy to active ingredient/excipients of ARV-471.
  • Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
  • Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study.
  • Concurrent administration of medications, foods or herbal supplements that are strong inhibitors or inducers of CYP3A4 and drugs with a known risk of causing Torsade de Pointes or QT interval prolongation. Prior use of strong CYP3A inhibitors and drugs with a known risk of causing Torsade de Pointes or QT interval prolongation must be stopped 7 days before enrollment and strong CYP3A inducers must be stopped 14 days before enrollment.
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  • Prior treatment with ARV-471.
  • Systemic anticancer therapy chemotherapy or endocrine therapy within 14 days prior to study entry (6 weeks for mitomycin C or nitrosoureas). If the last immediate anticancer treatment contained an antibody-based agent(s) (approved or investigational), then an interval of 28 days or 5 half-lives (whichever is shorter) of the agent(s) prior to receiving the study intervention treatment is required.
  • Participants who have initiated therapy with bone-modifying agents (bisphosphonates, denosumab, or similar) within 14 days of enrollment.
  • Previous high-dose chemotherapy requiring stem cell rescue.
  • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry. A participant may be eligible even if they are in the follow-up phase of an investigational study as long as they haven't received treatment in the study for 5 half lives of the agents.
  • Serum pregnancy test (for females of childbearing potential) positive at screening and/or a breastfeeding participant.
  • Participants with active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and known Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS)-related illness.
  • Baseline standard 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
  • Any of the following in the previous 12 months: myocardial infarction, long QT syndrome, Torsade de Pointes, clinically important atrial or ventricular arrhythmias, serious conduction system abnormalities, unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thrombo-embolic disease. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade . If a participant has a cardiac rhythm device/pacemaker placed and QTcF >470 ms, the participant may be considered eligible. Participants with cardiac rhythm device/pacemaker must be discussed in detail with the sponsor to judge eligibility.
  • History of symptomatic cardiac valve disease.
  • Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.

Trial locations and contacts

3 sites in 1 country.

Japan3 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • Aichi Cancer Center Hospital

    Nagoya, Aichi-ken, 464-8681

Other trials in Japan

About this study

Official title: A PHASE I, OPEN-LABEL STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF ARV-471 (PF-07850327), A SINGLE AGENT IN JAPANESE PARTICIPANTS WITH ER+/HER2-LOCALLY ADVANCED OR METASTATIC BREAST CANCER

The purpose of this clinical trial is to learn about the safety, tolerability, Pharmacokinetics (PK), and preliminary efficacy of ARV-471 as monotherapy in Japanese participants with ER+/HER2- locally advanced or metastatic breast cancer (mBC).

Being tested
vepdegestrant
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vepdegestrantDrug

    Also called ARV-471, PF-07850327

    ARV-471 will be administered orally QD with food, in continuous dosing over 28-day cycles.

Study groups in NCT05463952
Study groupRoleWhat they receive
vepdegestrantExperimentalDaily oral dosages of vepdegestrant
Receives: Drug: vepdegestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose Limiting Toxicity (DLTs) During First Treatment Cycle

    DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to ARV-471 and assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.

    Measured: Cycle 1 (28 days)

Secondary outcomes (20)

  1. Number of Participants With AEs and Serious AEs (SAEs)- All Causalities and Treatment Related

    An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. SAE was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly, a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic.

    Measured: Day 1 of study treatment up to 35 days after last dose of study treatment (approximately 1.5 years)

  2. Number of Participants With Laboratory Hematology Results by Maximum National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade

    The following hematology parameters were assessed: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related).

    Measured: During study treatment, approximately 1.5 years

  3. Number of Participants With Laboratory Chemistry Results by Maximum NCI-CTCAE Grade

    The following chemistry parameters were assessed: aspartate transaminase (AST), alkaline phosphatase (ALP), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate, creatinine kinase (CK), amylase and lipase. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related).

    Measured: During study treatment, approximately 1.5 years

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (AUCtau) of ARV 471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  5. Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  6. Maximum Observed Plasma Concentration (Cmax) of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  7. Time to Reach Maximum Concentration (Tmax) of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  8. Terminal Elimination Half-Life (t1/2) of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  9. Metabolite Ratio for Cmax (MRCmax)

    Measured: Through the end of the study treatment (approximately 1.5 years)

  10. Metabolite Ratio for AUCtau (MRAUCtau)

    Measured: Through the end of the study treatment (approximately 1.5 years)

  11. Lowest Concentration Observed During the Dosing Interval (Cmin) of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  12. Pre-dose Plasma Concentration (Ctrough) of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  13. Apparent Total Clearance (CL/F) of ARV-471

    Measured: Through the end of the study treatment (approximately 1.5 years)

  14. Apparent Volume of Distribution (Vz/F) of ARV-471

    Measured: Through the end of the study treatment (approximately 1.5 years)

  15. Effective Half-Life Based on Accumulation Ratio (t½Eff) of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  16. Accumulation Ratio (Rac) Based on AUC of ARV-471 and ARV-473

    Measured: Through the end of the study treatment (approximately 1.5 years)

  17. Objective Response Rate (ORR)

    ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) as per Response Evaluation Criteria in Solid Tumours (RECIST version [v] 1.1). BOR: best response was recorded from start of study treatment until disease progression or death due to any cause. CR: complete disappearance of all target lesions with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). PR: greater than or equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all targets measurable lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. All target lesions were assessed.

    Measured: From start of study treatment until disease progression or death due to any cause (approximately 1.5 years)

  18. Clinical Benefit Response (CBR)

    CBR is defined as the percentage of participants with BOR of CR, PR and stable disease (SD) of 24 weeks duration or longer. As per RECIST v1.1. SD: Does not qualify for CR, PR or Progression. All target lesions must be assessed. Stable could follow PR only in the rare case that the sum increased by <20% from the nadir, but enough that a previously documented 30% decrease no longer held. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal short axis <10 mm). No new lesions. PR: >= 30% decrease under baseline of sum of diameters of all targets measurable lesions. Short diameter was used in sum for target nodes, while longest diameter was used in sum for all other target lesions.

    Measured: From start of study treatment until disease progression or death due to any cause (approximately 1.5 years)

  19. Progression Free Survival (PFS)

    PFS was defined as the time from first dose of study treatment (ie, start date) to the date of progression of disease (PD) or death due to any cause, whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to an event, or for participants with an event after two or more missing tumor assessments. PD as per RECIST v1.1 for target lesions was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. For non-target lesions- PD was defined as unequivocal progression of pre-existing lesions. Analysis was performed using Kaplan-Meier method.

    Measured: From start of study treatment until disease progression or death due to any cause or censoring date (approximately 1.5 years)

  20. Duration of Response (DOR)

    Duration of response was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first in participants with confirmed objective response (CR or PR). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. Analysis was performed using Kaplan-Meier method.

    Measured: From the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause (approximately 1.5 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2022
  2. Study start16 Aug 2022
  3. Primary completion4 May 2023
  4. Study completion31 Mar 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05463952
Sponsor's protocol ID
C4891016
Status last verified
Oct 2024
First submitted
14 Jul 2022
Last updated
13 Nov 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Iwata H, Naito Y, Hattori M, Yoshimura A, Yonemori K, Aizawa M, Mori Y, Yoshimitsu J, Umeyama Y, Mukohara T. Safety and pharmacokinetics of vepdegestrant in Japanese patients with ER+ advanced breast cancer: a phase 1 study. Int J Clin Oncol. 2025 Jan;30(1):72-82. doi: 10.1007/s10147-024-02648-3. Epub 2024 Nov 20.

    PubMed 39565495

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vepdegestrant in people with Breast Neoplasms, run by Pfizer at 3 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicity (DLTs) During First Treatment Cycle (time frame: Cycle 1 (28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05463952, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2024; AzTrials last refreshed its copy on 30 Oct 2026.

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