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

NCT05463952 | Active Not Recruiting Phase 1 Results

• 1 other identifier: C4891016
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (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.

  Cycle 1 (28 days)

Secondary Outcomes (20)

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

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

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

  During study treatment, approximately 1.5 years

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

  During study treatment, approximately 1.5 years

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

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

• 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

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

Study Arms (1)

vepdegestrant

EXPERIMENTAL

Daily oral dosages of vepdegestrant

Drug: vepdegestrant

Interventions

vepdegestrant DRUG

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

Also known as: ARV-471, PF-07850327

vepdegestrant

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (3)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Related Publications (1)

• 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.

  PMID: 39565495 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquires@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 19, 2022
• Study Start: August 16, 2022
• Primary Completion: May 4, 2023
• Study Completion: March 31, 2025
• Last Updated: November 13, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3)