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

Phase 1Active Not RecruitingNCT05463952

Pfizer6 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Neoplasms

Interventions

vepdegestrantDRUG

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

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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.

Locations (3)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Outcomes

Primary Outcomes

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.

Time frame: Cycle 1 (28 days)

Secondary Outcomes

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.

Time frame: 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

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).

Time frame: During study treatment, approximately 1.5 years

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

Data from ClinicalTrials.gov

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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).

Time frame: 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