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NCT Number: NCT07062965

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.

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Disease Attributes Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Skin Diseases Skin and Connective Tissue Diseases Unilateral Breast Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

ICON Cancer Centre - Kurralta Park, Kurralta Park, South Australia, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-07248144

Drug

KAT6 inhibitor

Fulvestrant

Drug

Endocrine therapy

Everolimus

Drug

mTOR inhibitor

Exemestane

Drug

Endocrine therapy

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

    Time frame: From the date of randomization until disease progression or death due to any cause (up to approximately 2 years)

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: From the date of randomization until death due to any cause (up to approximately 5 years).

  2. Number of Participants with Objective Response (OR) by BICR

    Time frame: From the date of randomization until disease progression or death due to any cause (up to approximately 2 years)

  3. Duration of Response (DoR) as defined by BICR

    Time frame: 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.

  4. Number of Participants With Clinical Benefit Response (CBR) by BICR

    Time frame: From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) up to approximately 2 years.

  5. Number or Patients with Adverse Events (AEs) by Type

    Time frame: From screening until 28 days after the last dose, to approximately 5 years

  6. Number or Patients with AEs by Incidence

    Time frame: From screening until 28 days after the last dose, to approximately 5 years

  7. Number or Patients with AEs by Seriousness

    Time frame: From screening until 28 days after the last dose, to approximately 5 years

  8. Number or Patients with AEs by relationship to study interventions

    Time frame: From screening until 28 days after the last dose, to approximately 5 years

  9. Number of Participants With Abnormal Electrocardiogram (ECG; Arm A and B)

    Time frame: From screening until 28 days after the last dose, to approximately 5 years

  10. Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval (Arm A only)

    Time frame: 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.

  11. Number of Participants With Laboratory Test Abnormalities

    Time frame: From screening until 28 days after the last dose, to approximately 5 years

  12. Ctrough of PF-07248144

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Pfizer CT.gov Call Center

CONTACT

[email protected]

1-800-718-1021

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2030
First posted
Jul 14, 2025
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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