A Study to Learn About the Study Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Advanced Breast Cancer in China

Pfizer9 enrolled

Overview

The purpose of this clinical trial is to learn about the pharmacokinetics. safety and tolerability of the study medicine (called ARV-471) for the potential treatment of advanced estrogen receptor postive and human epidermal growth factor receptor 2 negative breast cancer. This study is seeking participants have * ER+/HER2- advanced breast cancer * received at least 1 line of endocrine therapy with or without CDK4/6 inhibitor * received up to 2 prior regimens of chemotherapy for advanced setting. All participants in this study will receive ARV-471. ARV-471 will be given by mouth at home once a day. The experiences of people receiving the study medicine will be examined. This will help determine if the study medicine is safe and effective. Participants will take part in this study until their cancer is no longer responding. During this time, they will have visits at the study clinic about every 4 weeks.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histological or cytological diagnosis of breast cancer with evidence of ER+/HER2- locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent. * Received at least 1 line of SOC of endocrine therapy with or without CDK4/6 inhibitor for locally advanced or metastatic disease. * Up to 2 prior regimens of chemotherapy for advanced or metastatic disease setting are allowed. Exclusion Criteria: * Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and clinically stable (including patients with residual CNS symptoms/deficits) off enzyme-inducing anticonvulsants and steroids for at least 28 days prior to first dose of study drug. * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism or other clinically significant episode of thromboembolic disease, congenital long QT syndrome, Torsade de Pointes, serious conduction system abnormalities (eg, bifascicular block defined as right bundle branch and left anterior or posterior hemiblock, 3rd degree AV block), clinically important arrhythmias, left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade.

Locations (3)

Cancer Hospital Chinese Academy of Medical Science

Beijing, Beijing Municipality, China

Jilin Province Tumor Hospital

Changchun, Jilin, China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Outcomes

Primary Outcomes

Single dose Cmax (Maximum plasma concentration)

Maximum plasma concentration

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose up to Day 2

Single dose AUCtau

Area under the concentration-time profile from time zero to time tau (τ), the dosing interval, where tau = 24 hours (QD dosing)

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Multiple dose Cmax

Maximum Observed Plasma Concentration (Cmax)

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Multiple dose AUCtau

Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Secondary Outcomes

Objective Response Rate - Percentage of Participants With Objective Response

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.1: 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 Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).

Time frame: Baseline up to 24 weeks

Percentage of Participants With Clinical Benefit

Percent of participants with confirmed complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks on study according to RECIST. Per RECIST v1.1: 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 axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as not qualifying for CR, PR, Progressive Disease (PD).

Time frame: Baseline up to 24 weeks

Duration of Objective Response (DOR)

DOR: time from date of first documented response (CR or PR) to first documented progression or death due to underlying cancer. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs; b) PR: \>=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: \>=20% increase in sum of diameter of all measured target lesions taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of \>=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion. If a participant with a CR or PR had no PD or death due to underlying cancer, participants was censored at date of last adequate tumor assessment.

Time frame: From the date of first documented response (CR or PR) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks

Presence (rate) or absence of blood biomarkers

To identify biomarkers (ESR1 mutation) of complete response and progression if occurs

Time frame: immediately after the end of treatment

Number of Participants With Notable Electrocardiogram (ECG) Values

Criteria for notable ECG values were as follow: QT interval (in millisecond \[msec\]) new (newly occurring post-baseline value) greater than (\>) 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; heart rate in bpm new (newly occurring post-baseline value) \<60 and \>100.

Time frame: From baseline up to 28 days after last dose of study drug

Number of Participants With Laboratory Abnormalities

Hemoglobin (HGB),hematocrit,erythrocytes (ery.),HDL cholesterol (chl.)\<0.8\*lower limit of normal(LLN);reticulocytes (ret.), ret./ery. (%)\<0.5\*LLN,\>1.5\*upper limit of normal (ULN);ery. mean corpuscular (EMC) volume,EMC HGB,EMC HGB

Time frame: Baseline (Day 1) up to at least 28 days after last dose of study drug

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs was determined at the investigator's discretion.

Time frame: Baseline up to 28 days after last dose of study drug

Number of Participants With Adverse Events (AEs) by type, frequency, severity (as graded by NCI CTCAE verision 5.0), timing, seriousness and relationship to study treatment

Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to \[study drug\] was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE.

Time frame: Baseline up to 28 days after the last dose of study drug

Single dose Tmax

Time at which Cmax occurred

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Single dose AUClast

Area under the concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Single dose MRCmax

ARV-473 to ARV-471 ratio for Cmax

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Single dose AUCinf

Area under the concentration-time profile from time zero extrapolated to infinite time

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Single dose CL/F

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Single dose Vz/F

Apparent volume of distribution

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Single dose t½

Terminal half-life

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Multiple dose Tmax

Time to Reach Maximum Observed Plasma Concentration

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Multiple dose Vz/F

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Multiple dose MRCmax

ARV-473 to ARV-471 ratio for Cmax

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Rac

Accumulation ratio based on AUC (observed)

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

t½eff

Effective half-life (t½eff) based on accumulation ratio

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Multiple dose CL/F

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Multiple dose t½

Terminal half-life

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Single dose MRAUCtau

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2

Multiple dose AUClast

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Multiple dose Cmin

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71

Multiple dose Ctrough

Time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71