NCT07062965|RecruitingPhase 3DMCFDA Drug

A 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.

An Interventional, Open-Label, Randomized, Multicenter, Phase 3 Study of PF-07248144 Plus Fulvestrant Compared to Investigator's Choice of Therapy in Adult Participants With Hormone Receptor-Positive, HER2-Negative Advanced/Metastatic Breast Cancer Whose Disease Progressed After Prior CDK4/6 Inhibitor-based Therapy

Pfizer ClinicalTrials.gov

Compare

2 other identifiers

C45510022025-520566-22-00

Study Type

interventional

Target

400

Locations

27 countries

Sites

202

Timeline

RegisteredJul 2025

StartedAug 2025

CompletionNov 2030

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

400

participants targeted

Target at P50-P75 for phase_3 breast-cancer

Timeline

55mo left

Started Aug 2025

Geographic Reach

27 countries

202 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.3 years study duration

Study Progress14%

Aug 2025Nov 2030

First Submitted

Initial submission to the registry

July 3, 2025

Completed

11 days until next milestone

First Posted

Study publicly available on registry

July 14, 2025

Completed

22 days until next milestone

Study Start

First participant enrolled

August 5, 2025

Completed

2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 22, 2027

Expected

3.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 4, 2030

Last Updated

May 6, 2026

Status Verified

May 1, 2026

Enrollment Period

2 years

First QC Date

July 3, 2025

Last Update Submit

May 4, 2026

Conditions

Breast Cancer

Keywords

Locally advanced or metastatic breast cancerEstrogen receptor positive [ER(+)]Progesterone receptor positive [PR(+)]Human epidermal growth factor receptor 2 negative [HER2(-)]ER(+)/HER2(-)PR(+)/HER2(-)HR(+)/HER2(-)Advanced Breast CancerBreast tumorBreast cancerEverolimusExemestaneFulvestrantMetastatic breast cancerEndocrine TherapyHormone TherapyHormone positive breast cancerRecurrent breast cancerHR+HER2-negativeRelapseRecurrentSecond line treatmentThird line treatmentLeft Sided Breast CancerRight Sided Breast CancerUnilateral Breast CancerCancer of the BreastCDK4/6iCDK4/6i-based TherapyBilateral Breast CancerProgression After CDK4/6i-based therapy

Outcome Measures

Primary Outcomes (1)

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 Outcomes (12)

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
+7 more secondary outcomes

Study Arms (2)

Arm A: PF-07248144 plus fulvestrant

OTHER

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

Drug: PF-07248144Drug: Fulvestrant

Arm B: everolimus plus ET

ACTIVE COMPARATOR

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.

Drug: FulvestrantDrug: EverolimusDrug: Exemestane

Interventions

PF-07248144DRUG

KAT6 inhibitor

Arm A: PF-07248144 plus fulvestrant

FulvestrantDRUG

Endocrine therapy

Arm A: PF-07248144 plus fulvestrantArm B: everolimus plus ET

EverolimusDRUG

mTOR inhibitor

Arm B: everolimus plus ET

ExemestaneDRUG

Endocrine therapy

Arm B: everolimus plus ET

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (202)

Ironwood Cancer & Research Centers

Chandler, Arizona, 85224, United States

RECRUITING

Ironwood Cancer & Research Centers

Gilbert, Arizona, 85297, United States

RECRUITING

Ironwood Cancer & Research Centers

Glendale, Arizona, 85306, United States

RECRUITING

Ironwood Cancer & Research Centers

Goodyear, Arizona, 85395, United States

RECRUITING

Ironwood Cancer & Research Centers

Mesa, Arizona, 85202, United States

RECRUITING

Ironwood Cancer & Research Centers

Mesa, Arizona, 85206, United States

RECRUITING

Ironwood Cancer & Research Centers

Phoenix, Arizona, 85028, United States

RECRUITING

Ironwood Cancer & Research Centers

Scottsdale, Arizona, 85260, United States

RECRUITING

Ventura County Hematology Oncology Specialists

Camarillo, California, 93010, United States

NOT YET RECRUITING

Los Angeles Cancer Network - (Admin Only / Central IDS) - No Patients

Glendale, California, 91204, United States

NOT YET RECRUITING

Los Angeles Cancer Network - Good Samaritan

Los Angeles, California, 90017, United States

NOT YET RECRUITING

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, 90017, United States

NOT YET RECRUITING

Rolling Oaks Radiology - Oxnard

Oxnard, California, 93030, United States

NOT YET RECRUITING

Ventura County Hematology Oncology Specialists

Oxnard, California, 93030, United States

NOT YET RECRUITING

Dr. Manoj Khatore, MD, FACC (Cardiology Practice)

Oxnard, California, 93036, United States

NOT YET RECRUITING

Ventura County Hematology Oncology Specialists

Ventura, California, 93003, United States

NOT YET RECRUITING