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PF-07248144 plus fulvestrant for HR-positive, HER2-negative advanced or metastatic breast cancer after prior 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

Phase 3 Interventional Pfizer · NCT07062965

This will test whether adding the experimental drug PF-07248144 to fulvestrant helps people with HR-positive, HER2-negative advanced or metastatic breast cancer who have progressed after prior therapies, including CDK4/6 inhibitors.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment400 (estimated)
Ages18 Years and up
SexAll
SponsorPfizer Industry-sponsored
Drugs / interventionschemotherapy, radiation
Locations202 sites (Chandler, Arizona and 201 other locations)
Trial IDNCT07062965 on ClinicalTrials.gov

What this trial studies

This is a Phase 3 interventional trial testing the combination of the investigational agent PF-07248144 with fulvestrant in people with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer. Eligible participants have measurable disease or bone-only disease, ECOG performance status 0–1, and progression after prior lines of therapy including CDK4/6 inhibitors. The trial will collect safety and effect data to determine whether the combination improves outcomes compared with existing options. Patients with documented PIK3CA, AKT1, or PTEN alterations are excluded, and the trial is conducted at Ironwood Cancer & Research Centers in the Phoenix, Arizona area.

Who should consider this trial

Good fit: Ideal candidates are people with HR-positive, HER2-negative locally advanced or metastatic breast cancer, measurable disease or bone-only metastases, ECOG 0–1, and prior progression after CDK4/6 inhibitor–containing therapy who do not have PIK3CA/AKT1/PTEN alterations.

Not a fit: Patients with detectable PIK3CA, AKT1, or PTEN alterations, poor performance status (ECOG >1), HER2-positive disease, or earlier-stage disease are unlikely to be eligible or to benefit from this regimen.

Why it matters

Potential benefit: If successful, this combination could slow tumor growth and extend the time patients live without their cancer progressing after prior therapy.

How similar studies have performed: Other trials combining endocrine therapy with targeted agents (CDK4/6, mTOR, PI3K inhibitors) have shown benefit in HR-positive, HER2-negative breast cancer, but PF-07248144 itself is experimental and not yet proven.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Chandler, Arizona and 201 other locations

+152 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Breast CancerLocally advanced or metastatic breast cancerEstrogen receptor positive [ER]Progesterone receptor positive [PR]Human epidermal growth factor receptor 2 negative [HER2]ER/HER2PR/HER2HR/HER2
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.