Recruiting

Phase 3

PF-07248144 & FulvestrantA Study to Learn About the Study Medicine Called PF-07248144 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment.

Sponsor:

Pfizer

Code:

NCT07062965

Conditions

Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

PF-07248144

Fulvestrant

Everolimus

Exemestane

Study Details

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.

Conditions

Breast Cancer

Study ID

NCT07062965

Start date

Aug 5, 2025

Status verified date

Oct, 2026

Completion date

Nov 4, 2030

Anticipated

Primary completion date

Jul 22, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

400 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Arm A: PF-07248144 plus fulvestrant

PF-07248144 tablet taken by mouth plus fulvestrant taken as a shot into the muscle.

active comparator: Arm B: everolimus plus ET

Everolimus tablet taken by mouth plus investigator's choice of endocrine therapy of exemestane tablet taken by mouth or fulvestrant taken as a shot into the muscle.

Interventions

PF-07248144

KAT6 inhibitor

Fulvestrant

Endocrine therapy

Everolimus

mTOR inhibitor

Exemestane

Endocrine therapy

Primary outcome measure

Progression Free Survival (PFS) as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: From the date of randomization until disease progression or death due to any cause (up to approximately 2 years) ]

Central Contacts and Locations

Central contacts

Pfizer CT.gov Call Center

1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations

Alaska Oncology and Hematology, LLC

Recruiting

Anchorage, Alaska, United States, 99508

Ironwood Cancer & Research Centers

Recruiting

Chandler, Arizona, United States, 85224

Banner Gateway Medical Center

Recruiting

Gilbert, Arizona, United States, 85234

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

Ironwood Cancer & Research Centers

Recruiting

Gilbert, Arizona, United States, 85297

Ironwood Cancer & Research Centers

Recruiting

Glendale, Arizona, United States, 85306

Ironwood Cancer & Research Centers

Recruiting

Goodyear, Arizona, United States, 85395

Ironwood Cancer & Research Centers

Recruiting

Mesa, Arizona, United States, 85202

Ironwood Cancer & Research Centers

Recruiting

Mesa, Arizona, United States, 85206

Ironwood Cancer & Research Centers

Recruiting

Phoenix, Arizona, United States, 85028

Ironwood Cancer & Research Centers

Recruiting

Scottsdale, Arizona, United States, 85260

Highlands Oncology Group, PA

Recruiting

Fayetteville, Arkansas, United States, 72703

Highlands Oncology Group, PA

Recruiting

Rogers, Arkansas, United States, 72758

Highlands Oncology Group, PA

Recruiting

Springdale, Arkansas, United States, 72762

Oncura Health - Anaheim

Recruiting

Anaheim, California, United States, 92805

Ventura County Hematology Oncology Specialists

Recruiting

Camarillo, California, United States, 93010

Oncura Health - Fountain Valley

Recruiting

Fountain Valley, California, United States, 92708

Oncura Health - Corporate (Central IDS & Regulatory Only)

Recruiting

Glendale, California, United States, 91204

Oncura Health - Good Samaritan

Recruiting

Los Angeles, California, United States, 90017

Dr. Karandeep Singh MD

Recruiting

Oxnard, California, United States, 93030

Rolling Oaks Radiology - Oxnard

Recruiting

Oxnard, California, United States, 93030

Ventura County Hematology Oncology Specialists

Recruiting

Oxnard, California, United States, 93030

Rolling Oaks Radiology North Solar

Recruiting

Oxnard, California, United States, 93036

Clinical and Translational Research Unit (CTRU)

Recruiting

Palo Alto, California, United States, 94304

Stanford Cancer Center

Recruiting

Palo Alto, California, United States, 94304

Stanford Women's Cancer Center

Recruiting

Palo Alto, California, United States, 94304

Sansum Clinic

Recruiting

Santa Barbara, California, United States, 93105

Sansum Clinic

Recruiting

Solvang, California, United States, 93463

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Recruiting

Torrance, California, United States, 90502

Torrance Memorial Physician Network - Cancer Care

Recruiting

Torrance, California, United States, 90505

Torrance Memorial Physician Network-Cancer Care

Recruiting

Torrance, California, United States, 90505

Harbor-UCLA Medical Center

Recruiting

Torrance, California, United States, 90509

Oncura Health - Valley Presbyterian

Recruiting

Van Nuys, California, United States, 91405

Ventura County Hematology Oncology Specialists

Recruiting

Ventura, California, United States, 93003