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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

Geo Regions

Category

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.

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

Phase 1

NCT05463952

Active Not-enrolling

Globe

Locations

Japan

Study design
Participant Group/Arm

EXPERIMENTAL: ARV-471

Daily oral dosages of ARV-471

Intervention/Treatment

DRUG: ARV-471

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

Study design table for Clinical Trial
Key eligibility criteria
Inclusion criteria

1. Participants (women and men) at least 20 years of age at the time of signing the informed consent. 2. Histological or cytological diagnosis of ER+/HER2- advanced breast cancer that is metastatic, recurrent, or locally advanced unresectable breast cancer. 3. Participants who are resistant to standard therapy or for which no standard therapy is available or have received. 4. 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. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. 6. Adequate Bone Marrow or Coagulation Function. 7. Adequate Renal Function, defined as an estimated creatinine clearance ≥60 mL/min as calculated using the method standard for the institution. 8. Adequate Liver Function. 9. Participants with brain metastases must meet all the specified conditions. 10. Resolution of acute effects of any prior therapy to either baseline severity or CTCAE version 5.0 Grade ≤1.

Exclusion criteria

1. 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. 2. 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. 3. Known or suspected hypersensitivity or severe allergy to active ingredient/excipients of ARV-471. 4. 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. 5. 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. 6. 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. 7. Prior treatment with ARV-471. 8. 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. 9. Participants who have initiated therapy with bone-modifying agents (bisphosphonates, denosumab, or similar) within 14 days of enrollment. 10. Previous high-dose chemotherapy requiring stem cell rescue. 11. 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. 12. Serum pregnancy test (for females of childbearing potential) positive at screening and/or a breastfeeding participant. 13. 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. 14. Baseline standard 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results. 15. 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. 16. History of symptomatic cardiac valve disease. 17. Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.

Key dates
Study start date
  • August 2022
Estimated Study Completion Date
  • March 2024
Key endpoints
Primary Outcome Measures
Outcome Measure

Dose Limited Toxicities (DLTs)

Measure Description

Number of participants with dose-limiting toxicities (DLTs)

Time Frame

Time Frame: Up to 29 days

Primary Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

Safety and Tolerability as assessed by adverse event monitoring for participants.

Measure Description

Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

Time Frame

Up to 24 months

Outcome Measure

Safety and Tolerability through monitoring of laboratory assessments for participants.

Measure Description

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Time Frame

Up to 24 months

Outcome Measure

Single Dose: AUC from time zero to time tau (AUCtau)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Single Dose: AUC from time zero to time of last measurable concentration (AUClast)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Single Dose: Maximum Observed Concentration (Cmax)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Single Dose: Time to Maximum concentration (Tmax)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Single Dose: Terminal Elimination half-life (t1/2)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Single Dose: Metabolite Ratio Cmax (MRCmax)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: AUC from time zero to time tau (AUCtau)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: AUC from time zero to time of last measurable concentration (AUClast)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Maximum Observed Concentration (Cmax)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Minimum Observed Concentration (Cmin)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Trough Observed Concentration (Ctrough)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Apparent total clearance (CL/F)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Time to Maximum concentration (Tmax)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Apparent volume of distribution (Vz/F)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: accumulation ratio based on AUC (observed) (Rac)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Terminal Elimination half-life (t1/2)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Effective half-life based on accumulation ratio (t½eff)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Metabolite Ratio Cmax (MRCmax)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Multiple Dose: Metabolite Ratio AUCtau (MRAUCtau)

Measure Description

Pharmacokinetic (PK) assessments for ARV-471 and ARV-473 (an epimer of ARV-471)

Time Frame

Up to 24 months

Outcome Measure

Overall Response Rate (ORR) in participants

Measure Description

Time Frame

Up to 24 months

Outcome Measure

Clinical Benefit Response (CBR) based on the summation of complete Response (CR), Partial Response (PR) and Stable Disease (SD) of 24 weeks duration or longer in participants

Measure Description

Time Frame

Up to 24 months

Outcome Measure

Progression Free Survival (PFS) observed in participants

Measure Description

Time Frame

Up to 24 months

Outcome Measure

Duration of Response (DOR) in participants

Measure Description

Time Frame

Up to 24 months

Secondary Outcome Measures table for Clinical Trial
Number of participants

6

Collaborators and investigators

Sponsor: Pfizer

Collaborator: Arvinas Estrogen Receptor, Inc.

This information is current as of September 18th 2023.

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More Information Close 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. NCT05463952