Recruiting 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.

Phase III Interventional Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: PF-07248144, Fulvestrant, Everolimus, Exemestane.
Who it may be relevant to: Registry conditions: Breast Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Belgium, Brazil, Bulgaria +22
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official 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

Overview

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.

Interventions

Drug PF-07248144
KAT6 inhibitor
Drug Fulvestrant
Endocrine therapy
Drug Everolimus
mTOR inhibitor
Drug Exemestane
Endocrine therapy

Primary outcome measures

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 outcome measures (12)

Overall Survival (OS) [Time frame: From the date of randomization until death due to any cause (up to approximately 5 years).]
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)]
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.]
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.]
Number or Patients with Adverse Events (AEs) by Type [Time frame: From screening until 28 days after the last dose, to approximately 5 years]
Number or Patients with AEs by Incidence [Time frame: From screening until 28 days after the last dose, to approximately 5 years]
Number or Patients with AEs by Seriousness [Time frame: From screening until 28 days after the last dose, to approximately 5 years]
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]
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]
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]
Number of Participants With Laboratory Test Abnormalities [Time frame: From screening until 28 days after the last dose, to approximately 5 years]
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]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment