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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Nov 2025 → ongoing

Decision date (initial)

2025-10-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Efficacy, Safety

To demonstrate superiority of PF-07248144 plus fulvestrant (Arm A) versus ICT (Arm B) with respect to progression-free survival (PFS).

Secondary objectives 4

1. To compare Arm A versus Arm B with respect to overall survival (OS)
2. To assess Arm A versus Arm B with respect to measures of tumor control and to evaluate duration of response (DoR) within each treatment arm
3. To assess safety and tolerability in Arm A and Arm B
4. To characterize trough plasma concentrations of PF-07248144 when given in combination with fulvestrant

Conditions and MedDRA coding

Hormone Receptor-Positive, HER2-Negative Advanced/Metastatic Breast Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical trials/trial data and results/data requests. URL: https://www.pfizer.com/science/clinical trials/trial data and results/data requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. At least 18 years of age (or the minimum age of consent in accordance with local regulations) at screening.
2. Histological confirmation 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.
3. Must have received prior CDK4/6 inhibitor in one of the following settings as described below: i) CDK4/6i plus ET in the A/mBC setting; or ii) Adjuvant CDK4/6i plus ET with documented PD/recurrence during or within 12 months after the last dose of CDK4/6i. • In addition, participants are eligible if they • Previously received CDK4/6i or ET as a monotherapy, or in combination for rechallenge therapy in the A/mBC setting Note: fulvestrant or exemestane is allowed, but not required • Have received prior therapy targeting estrogen receptor 1 (ESR1) or breast cancer gene (BRCA)1/2.
4. Must provide a sufficient amount of representative formalin fixed, paraffin embedded (FFPE) tumor tissue specimen.
5. Measurable disease or non-measurable bone only disease as defined by RECIST v1.1.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. Note: Participants with ECOG 2 may be considered eligible if, per the investigator’s judgement and sponsor’s agreement, the participant has adequate organ function, life expectancy, and meets other protocol eligibility.

Exclusion criteria 11

1. Documented detectable phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)/AKT serine/threonine kinase 1 (AKT1)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN) alterations.
2. Received greater than two prior lines of systemic therapy in the A/mBC setting.
3. Prior targeted therapy for one or more PIK3CA, AKT1, or PTEN alterations.
4. Had received any prior chemotherapy, including antibody drug conjugates (ADCs), in an A/mBC setting. Participants who have previously received chemotherapy in the (neo)adjuvant setting are not excluded from the study.
5. Major surgery within 4 weeks prior to randomization.
6. Systemic anti-cancer therapy or radiation within 2 weeks prior to randomization.
7. Visceral crisis or organ failure requiring immediate chemotherapy-based regimens (including antibody-drug conjugate [ADC]) or at risk of immediately life-threatening complications in the short term.
8. Any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study.
9. Known active uncontrolled or symptomatic central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease.
10. Current use or anticipated need for any prohibited food, supplements or concomitant medication(s) (ie, other anti-cancer therapies, other endocrine therapies, cytochrome P450 2C9 [CYP2C9] and P450 3A4/5 [CYP3A4/5] inhibitors and inducers).
11. Renal impairment, hepatic dysfunction, or hematologic abnormalities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS, defined as the time from the date of randomization to the date of first documented disease progression, as determined by blinded independent central review (BICR) per RECIST v1.1, or death due to any cause in the absence of progressive disease (PD), whichever occurs first.

Secondary endpoints 6

1. OS, defined as the time from the date of randomization to the date of death due to any cause.
2. Objective Response (OR) by BICR per RECIST v1.1
3. DoR by BICR per RECIST v1.1
4. Clinical Benefit Response (CBR: complete response [CR], partial response [PR], or stable disease [SD] /non-CR/non-progression [non-PD] ≥24 weeks) by BICR per RECIST v1.1
5. Type, incidence, severity (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE v5.0]), seriousness of adverse events (AEs), any laboratory test or electrocardiogram (ECG) abnormalities, and characterization PF-07248144 effect on corrected QT interval (QTc) from baseline.
6. Ctrough (lowest plasma concentration before scheduled dose) of PF-07248144

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 9

Locations

14 EU/EEA countries · 120 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 173 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

20 submissions — initial application plus substantial / non-substantial modifications