A Study of the Investigational Drug PF-07248144 in Combination with Fulvestrant in Patients with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer Following Prior Treatment with a CDK4/6 Inhibitor

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of breast cells. If cancer cells spread from the breast to distant organs such as the bones, lungs, liver, or brain and form new tumors there, the disease is referred to as metastatic. Some of these tumors are hormone receptor-positive, meaning the cancer cells have binding sites (receptors) on their surface for the female sex hormones estrogen and progesterone, and these hormones can promote the growth of the cancer cells. At the same time, the tumors may be HER2-negative, meaning that no or very few HER2 receptors—which are involved in regulating cell growth and division—are detectable on the cancer cells. For hormone receptor-positive, HER2-negative breast cancer that is already locally advanced or has metastasized, anti-hormone therapy is typically used first, often in combination with a CDK4/6 inhibitor. CDK4/6 inhibitors target the enzymes CDK4 and CDK6 and are designed to slow the division of cancer cells. If the disease progresses despite this treatment, options include combinations of everolimus and exemestane or other anti-hormone therapies such as fulvestrant. The investigational drug PF-07248144 is currently still being tested and belongs to a new class of drugs known as KAT6 inhibitors. The drug influences the activity of certain genes in the cancer cells. This is intended to prevent the tumor cells from multiplying further and cause them to enter a permanent dormant state, thereby slowing tumor growth.

The goal of this Phase 3 study is to investigate the efficacy and safety of the study drug PF-07248144 in combination with fulvestrant compared to a treatment selected by the study physicians. As part of the study, patients will be randomly assigned to two treatment groups. Arm A will receive PF-07248144 as a tablet along with fulvestrant as an intramuscular injection. Arm B receives everolimus as a tablet together with an anti-hormonal therapy selected by the study physicians (either exemestane as a tablet or fulvestrant as an intramuscular injection). The study is open-label, which means that both the patients and the study physicians know which treatment is being administered. The main goal (primary endpoint) of the study is progression-free survival for up to two years—that is, the time until the disease progresses or until death.

Eligible participants are patients aged 18 years or older with hormone receptor-positive, HER2-negative breast cancer that is locally advanced or metastatic, and whose disease has progressed during or within twelve months after prior treatment with a CDK4/6 inhibitor. There must be no indication for curative surgery or radiation therapy.