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.

Launched by PFIZER · Jul 3, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new medicine called PF-07248144 combined with fulvestrant to treat a certain type of advanced breast cancer. This breast cancer is called HR-positive, HER2-negative, which means the cancer cells grow in response to hormones like estrogen but do not have a protein called HER2 that some other breast cancers have. The study aims to find out if adding PF-07248144 to fulvestrant is safe and helps control cancer that has worsened after previous hormone-based treatments.

People who may join this study are adults whose breast cancer has progressed despite earlier treatment with a type of medicine called CDK4/6 inhibitors combined with hormone therapy. Participants will be randomly assigned to receive either the new combination of PF-07248144 (a daily pill) plus fulvestrant (given as injections in the clinic) or a standard treatment that includes everolimus plus hormone therapy (also taken as pills). The study will compare how well these treatments work and their side effects. If you join, you can expect to take some medicines at home daily and visit the clinic for injections and check-ups. This study is not yet recruiting but is looking for people who meet the specific health criteria described.

Gender

ALL

Eligibility 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.