Clinical trial NCT05732428: A Study to Learn About the Study Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Advanced Breast Cancer 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Arvinas Estrogen Receptor, Inc.
First posted: 2023-02-17
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Single dose Cmax (Maximum plasma concentration)
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose up to Day 2
measure: Single dose AUCtau
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Multiple dose Cmax
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Multiple dose AUCtau
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Secondary outcomes:
measure: Objective Response Rate - Percentage of Participants With Objective Response
timeFrame: Baseline up to 24 weeks
measure: Percentage of Participants With Clinical Benefit
timeFrame: Baseline up to 24 weeks
measure: Duration of Objective Response (DOR)
timeFrame: 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
measure: Presence (rate) or absence of blood biomarkers
timeFrame: immediately after the end of treatment
measure: Number of Participants With Notable Electrocardiogram (ECG) Values
timeFrame: From baseline up to 28 days after last dose of study drug
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline (Day 1) up to at least 28 days after last dose of study drug
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to 28 days after last dose of study drug
measure: 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
timeFrame: Baseline up to 28 days after the last dose of study drug
measure: Single dose Tmax
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Single dose AUClast
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Single dose MRCmax
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Single dose AUCinf
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Single dose CL/F
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Single dose Vz/F
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Single dose t½
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Multiple dose Tmax
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Multiple dose Vz/F
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Multiple dose MRCmax
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Rac
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: t½eff
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Multiple dose CL/F
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Multiple dose t½
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Single dose MRAUCtau
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
measure: Multiple dose AUClast
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Multiple dose Cmin
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
measure: Multiple dose Ctrough
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Changchun
country: China
facility: Jilin Province Tumor Hospital
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: