Back to resultsA Study to Learn About the Study Medicine (Called ARV-471) in People With ER+/HER2- Advanced BC in China
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ARV-471
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
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.
Sites / Locations
- Cancer Hospital Chinese Academy of Medical Science
- Jilin Province Tumor Hospital
- The First Affiliated Hospital of Xi'an Jiaotong University
- Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
- Cancer Hospital Chinese Academy of Medical Sciences
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ARV-471
Arm Description
Outcomes
Primary Outcome Measures
Single dose Cmax (Maximum plasma concentration)
Maximum plasma concentration
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)
Multiple dose Cmax
Maximum Observed Plasma Concentration (Cmax)
Multiple dose AUCtau
Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Secondary Outcome Measures
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).
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).
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.
Presence (rate) or absence of blood biomarkers
To identify biomarkers (ESR1 mutation) of complete response and progression if occurs
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.
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
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.
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.
Single dose Tmax
Time at which Cmax occurred
Single dose AUClast
Area under the concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)
Single dose MRCmax
ARV-473 to ARV-471 ratio for Cmax
Single dose AUCinf
Area under the concentration-time profile from time zero extrapolated to infinite time
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.
Single dose Vz/F
Apparent volume of distribution
Single dose t½
Terminal half-life
Multiple dose Tmax
Time to Reach Maximum Observed Plasma Concentration
Multiple dose Vz/F
Multiple dose MRCmax
ARV-473 to ARV-471 ratio for Cmax
Rac
Accumulation ratio based on AUC (observed)
t½eff
Effective half-life (t½eff) based on accumulation ratio
Multiple 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.
Multiple dose t½
Terminal half-life
Single dose MRAUCtau
Multiple dose AUClast
Multiple dose Cmin
Multiple dose Ctrough
Full Information
NCT ID
NCT05732428
First Posted
January 17, 2023
Last Updated
September 15, 2023
Sponsor
Pfizer
Collaborators
Arvinas Estrogen Receptor, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05732428
Brief Title
A Study to Learn About the Study Medicine (Called ARV-471) in People With ER+/HER2- Advanced BC in China
Official Title
A PHASE 1, OPEN LABEL STUDY EVALUATING THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF ARV-471 (PF-07850327) AS A SINGLE AGENT IN CHINESE PARTICIPANTS WITH ER+/HER2- ADVANCED BREAST CANCER
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 20, 2023 (Actual)
Primary Completion Date
November 19, 2023 (Anticipated)
Study Completion Date
November 7, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Arvinas Estrogen Receptor, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARV-471
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ARV-471
Intervention Description
ARV-471 will be administered orally once daily with food (eg, a light meal of approximately 400 to 600 calories which includes a mixture of fat carbohydrates, and protein) at RP3D for monotherapy defined in study ARV-471-mBC-101, in continuous dosing over 28-day cycles
Primary Outcome Measure Information:
Title
Single dose Cmax (Maximum plasma concentration)
Description
Maximum plasma concentration
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose up to Day 2
Title
Single dose AUCtau
Description
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
Title
Multiple dose Cmax
Description
Maximum Observed Plasma Concentration (Cmax)
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Title
Multiple dose AUCtau
Description
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 Outcome Measure Information:
Title
Objective Response Rate - Percentage of Participants With Objective Response
Description
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
Title
Percentage of Participants With Clinical Benefit
Description
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
Title
Duration of Objective Response (DOR)
Description
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
Title
Presence (rate) or absence of blood biomarkers
Description
To identify biomarkers (ESR1 mutation) of complete response and progression if occurs
Time Frame
immediately after the end of treatment
Title
Number of Participants With Notable Electrocardiogram (ECG) Values
Description
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
Title
Number of Participants With Laboratory Abnormalities
Description
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
Title
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description
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
Title
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
Description
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
Title
Single dose Tmax
Description
Time at which Cmax occurred
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
Title
Single dose AUClast
Description
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
Title
Single dose MRCmax
Description
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
Title
Single dose AUCinf
Description
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
Title
Single dose CL/F
Description
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
Title
Single dose Vz/F
Description
Apparent volume of distribution
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
Title
Single dose t½
Description
Terminal half-life
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
Title
Multiple dose Tmax
Description
Time to Reach Maximum Observed Plasma Concentration
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Title
Multiple dose Vz/F
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Title
Multiple dose MRCmax
Description
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
Title
Rac
Description
Accumulation ratio based on AUC (observed)
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Title
t½eff
Description
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
Title
Multiple dose CL/F
Description
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 71
Title
Multiple dose t½
Description
Terminal half-life
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Title
Single dose MRAUCtau
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
Title
Multiple dose AUClast
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Title
Multiple dose Cmin
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Title
Multiple dose Ctrough
Time Frame
0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Hospital Chinese Academy of Medical Science
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Facility Name
Jilin Province Tumor Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130000
Country
China
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710061
Country
China
Facility Name
Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
Facility Name
Cancer Hospital Chinese Academy of Medical Sciences
City
Shanghai
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
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.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4891018
Description
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Learn more about this trial
A Study to Learn About the Study Medicine (Called ARV-471) in People With ER+/HER2- Advanced BC in China
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