Breast Cancer
Conditions
Keywords
human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), HER2-negative, HR-Positive, Breast Cancer (BC), Neoadjuvant, Postmenopausal
Brief summary
The purpose of this study is to learn about the effects of the study medicine PF-07220060 plus letrozole, compared with the effects of taking letrozole alone without PF-07220060 for treatment of breast cancer. This study is seeking for participants who are: * women of age 18 years and older post menopause (either naturally or surgically). * confirmed to have Hormone receptor (HR) positive, Human epidermal growth factor receptor 2 (HER2) negative breast cancer. HER2 negative describes cells that have a small amount or none of a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that are HER2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface. * not been treated for their cancer before this study. Participants will be randomly assigned (like flipping a coin) to receive the treatment (PF-07220060 plus letrozole) or letrozole alone. Both PF-07220060 and letrozole are taken by mouth. PF-07220060 will be taken twice a day for 14 days. Letrozole will be taken once a day for 14 days. Participants will have a screening period for up to 28 days. If deemed fit, they will receive study treatment for 14 days, and then will have a follow-up visit about 28 days after their last dose. All participants will have at least one biopsy during the study. Biopsy is the removal of cells or tissues for examining. All participants will have a biopsy on Day 14. Additional assessments for safety including blood draws and interviews done by the site staff will be completed during the study.
Interventions
DRUGPF-07220060
PF-07220060 given as tablet by mouth twice a day for 14 days.
DRUGletrozole
Letrozole given as tablet by mouth once a day for 14 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women with histologically confirmed HR-positive and HER2-negative BC (per local assessment) * Documented by estrogen receptor (ER) and/or progesterone receptor (PR)-positive disease by IHC or ISH * Participants must have Ki-67 score \>/=10% with unilateral, invasive T1c-T4c, N0-N2, M0 BC * Participants must be willing and able to undergo a baseline and Day 14 biopsy and must have an ECOG PS or 0 or 1. * Participants must be treatment naive for the treatment of BC and cannot have had prior treatment with any systemic therapy (e.g., chemotherapy, hormonal therapy), radiation, surgery, or any investigational agents or use of hormone replacement therapy (HRT) or any other estrogen-containing medication (including vaginal estrogen) within 2 weeks prior to diagnostic tissue sample taken.
Exclusion criteria
* No prior systemic therapy, radiation, surgery, investigational therapy for treatment of breast cancer * Certain medical conditions in the previous 6 months, for example: 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, symptomatic pulmonary embolism or other clinically significant episode of thromboembolism * Lab abnormalities outside protocol specified parameters
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Ki-67 | Day 14 | Centrally assessed biopsy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Serious AEs | Baseline, Day 14, and Day 28 post last treatment follow-up visit | — |
| Incidence of AEs leading to Discontinuation | Baseline, Day 14, and Day 28 post last treatment follow-up visit | — |
| Incidence of Adverse Events (AEs) | Baseline, Day 14, and Day 28 post last treatment follow-up visit | — |
| Circulating tumor DNA (ctDNA) measurements | Baseline and Day 14 | Evaluate response on treatment |
| Percentage of Ki-67 | Screening and Day 14 | All participants will have Ki-67 staining from the biopsy sample on Day 14 and Screening if not previously available |
| Ctrough and peri-biopsy plasma concentrations of PF-07220060 | Pre-dose within 30 minutes and post-dose within 1 hour before or after biopsy | Ctrough was defined as pre-dose serum concentration during multiple dosing and observed directly from data. |
Countries
Australia, Belgium, France, Germany, Italy, Poland, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, United States
Outcome results
None listed