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

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

JPRN

Registry ID

JPRN-jRCT2031250245

Enrollment

400

Registered

2025-07-22

Start date

2025-08-05

Completion date

Unknown

Last updated

2026-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Interventions

Arm A: PF-07248144 plus fulvestrant Drug: PF-07248144 KAT6 inhibitor Drug: Fulvestrant Endocrine therapy Arm B: everolimus plus ET Drug: Everolimus mTOR inhibitor Drug: Fulvestrant Endocrine therapy D

Eligibility

Sex/Gender

All

Inclusion 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

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
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

Measure	Time frame
2. Overall Survival (OS) [Time Frame: From the date of randomization until death due to any cause (up to approximately 5 years).] 3. 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)] 4. 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.] 5. 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.] 6. Number or Patients with Adverse Events (AEs) by Type [Time Frame: From screening until 28 days after the last dose, to approximately 5 years] 7. Number or Patients with AEs by Incidence [Time Frame: From screening until 28 days after the last dose, to approximately 5 years] 8. Number or Patients with AEs by Seriousness [Time Frame: From screening until 28 days after the last dose, to approximately 5 years] 9. 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] 10. 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] 11. Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval (Arm A only) 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. [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] 12.	—

Measure

Time frame

2. Overall Survival (OS) [Time Frame: From the date of randomization until death due to any cause (up to approximately 5 years).] 3. 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)] 4. 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.] 5. 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.] 6. Number or Patients with Adverse Events (AEs) by Type [Time Frame: From screening until 28 days after the last dose, to approximately 5 years] 7. Number or Patients with AEs by Incidence [Time Frame: From screening until 28 days after the last dose, to approximately 5 years] 8. Number or Patients with AEs by Seriousness [Time Frame: From screening until 28 days after the last dose, to approximately 5 years] 9. 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] 10. 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] 11. Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval (Arm A only) 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. [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] 12.

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Countries

Australia, Belgium, Bulgaria, Canada, China, Czechia, Finland, Greece, India, Israel, Italy, Japan, Netherlands, Poland, Puerto Rico, Slovakia, South Korea, Spain, Sweden, Taiwan, United States

Contacts

Public ContactClinical Trials Information Desk

Pfizer R&D Japan G.K.

clinical-trials@pfizer.com+81-3-5309-7000

Outcome results

None listed

Source: JPRN (via WHO ICTRP) · Data processed: Jul 3, 2026