Breast Cancer
Conditions
Keywords
Locally advanced or metastatic breast cancer, Estrogen receptor positive [ER(+)], Progesterone receptor positive [PR(+)], Human epidermal growth factor receptor 2 negative [HER2(-)], ER(+)/HER2(-), PR(+)/HER2(-), HR(+)/HER2(-), Advanced Breast Cancer, Breast tumor, Breast cancer, Everolimus, Exemestane, Fulvestrant, Metastatic breast cancer, Endocrine Therapy, Hormone Therapy, Hormone positive breast cancer, Recurrent breast cancer, HR+, HER2-negative, Relapse, Recurrent, Second line treatment, Third line treatment, Left Sided Breast Cancer, Right Sided Breast Cancer, Unilateral Breast Cancer, Cancer of the Breast, CDK4/6i, CDK4/6i-based Therapy, Bilateral Breast Cancer, Progression After CDK4/6i-based therapy
Brief summary
The purpose of this study is to learn about the safety and effects of the study medicine PF-07248144 when given along with fulvestrant for the possible treatment of HR-positive, HER2-negative advanced or metastatic breast cancer. HR-positive breast cancer cells have proteins on their surface called receptors that bind to hormones like estrogen and progesterone (female sex hormones). These hormones can promote the growth of cancer cells. 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. Advanced cancer is a term that is often used to describe cancer that is unlikely to be cured. Metastatic cancer is the type where the cancer cells spread from one part of the body to another. This study is seeking for participants whose breast cancer has gotten worsen after receiving cyclin dependent kinase (CDK) 4/6 inhibitor-based therapy. Half of participants in this study will receive their usual study treatment, everolimus with endocrine therapy (either exemestane or fulvestrant) for HR-positive/HER2-negative advanced or metastatic breast cancer (A/mBC). The study doctor will discuss which hormone therapy is right for the participant before treatment begins. PF-07248144 is a tablet that will be taken by mouth at home every day in a 28-day cycle. Fulvestrant will be given as two injections (one injection in the buttock) at visits to the study clinic. Everolimus and exemestane are also tablets and will be taken by mouth at home every day in a 28-day cycle. The study will compare the experiences of people receiving PF-07248144 in combination with fulvestrant to those of the people who do not. This will help see if PF-07248144 in combination with fulvestrant is safe and effective.
Interventions
DRUGPF-07248144
KAT6 inhibitor
DRUGFulvestrant
Endocrine therapy
DRUGEverolimus
mTOR inhibitor
DRUGExemestane
Endocrine therapy
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Study participants will be randomly assigned into 1 of 2 groups in parallel for the entire duration of the study. The experimental arm will receive PF-07248144 and fulvestrant (Arm A) while the comparator arm will receive everolimus in combination with the study doctor's choice of endocrine therapy (exemestane or fulvestrant; Arm B).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of HR-positive HER2-negative breast cancer with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent. * Prior CDK4/6 inhibitor therapy in combination with endocrine therapy in advance metastatic setting or in adjuvant setting with documented progression during or within 12 months after the last dose of CDK4/6i. * Participants are eligible if they previously received CDK4/6i or ET as a monotherapy, or in combination for rechallenge therapy in the advance or metastatic setting; have received prior therapy targeting estrogen receptor 1 (ESR1) or breast cancer gene (BRCA)1/2. * Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
Exclusion criteria
* Documented detectable PIK3CA/AKT1/PTEN alterations in tissue * Received greater than two prior lines of systemic therapy in the advance or metastatic setting * Had received any prior chemotherapy, including antibody drug conjugates (ADCs), in advance or metastatic setting. Participants who have previously received chemotherapy in the (neo)adjuvant setting are not excluded from the study. * Any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study. * Renal impairment, hepatic dysfunction, or hematologic abnormalities.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | From the date of randomization until disease progression or death due to any cause (up to approximately 2 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the date of randomization until death due to any cause (up to approximately 5 years). | — |
| Number of Participants with Objective Response (OR) by BICR | From the date of randomization until disease progression or death due to any cause (up to approximately 2 years) | — |
| Duration of Response (DoR) as defined by BICR | From the date of the first objective (PR or CR) response (every 8 weeks during the first 48 weeks and then every 12 week) up to approximately 2 years. | — |
| Number of Participants With Clinical Benefit Response (CBR) by BICR | From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) up to approximately 2 years. | — |
| Number or Patients with Adverse Events (AEs) by Type | From screening until 28 days after the last dose, to approximately 5 years | — |
| Number or Patients with AEs by Incidence | From screening until 28 days after the last dose, to approximately 5 years | — |
| Number or Patients with AEs by Seriousness | From screening until 28 days after the last dose, to approximately 5 years | — |
| Number or Patients with AEs by relationship to study interventions | From screening until 28 days after the last dose, to approximately 5 years | — |
| Number of Participants With Abnormal Electrocardiogram (ECG; Arm A and B) | From screening until 28 days after the last dose, to approximately 5 years | — |
| Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval (Arm A only) | 0h pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 3 Day 1; additional 4 hrs post dose on Cycle 1 Day 15 and Cycle 2 Day 1 | The study includes a QTc sub-study in approximately 40 participants in Arm A enrolled at selected sites which will evaluate the effect of PF-07248144 on QTc interval via collection of triplicate ECGs (central reading) time-matched with pharmacokinetic (PK) draws. |
| Number of Participants With Laboratory Test Abnormalities | From screening until 28 days after the last dose, to approximately 5 years | — |
| Ctrough of PF-07248144 | Cycle 1 (Day 1), Cycle 1 (Day 15), Cycle 2 (Day 1), and Cycles 3, 5, and 7 (Day 1) only. Each Cycle is 28 days | Ctrough was defined as pre-dose serum concentration during multiple dosing and observed directly from data. |
Countries
Australia, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, Poland, Slovakia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed