A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Abemaciclib and Fulvestrant in HR+, HER2- Advanced or Metastatic Breast Cancer Post-CDK4/6 Inhibitor Therapy

The primary objective of this study is to compare the **efficacy** of **fulvestrant** with or without **abemaciclib** in participants with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced or metastatic **breast cancer** following progression on a CDK4 & 6 inhibitor and endocrine therapy. This comparison is clinically relevant as it aims to determine the potential benefit of adding abemaciclib to fulvestrant in improving outcomes for patients who have limited treatment options after progression on standard therapies.

The clinical trial involves a total of **193 participants** diagnosed with **breast neoplasm** and **neoplasm metastasis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including a diagnosis of HR+, HER2- locally advanced or metastatic breast cancer, and evidence of disease progression or recurrence. The trial population is characterized by individuals who have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must have adequate renal, hematologic, and hepatic organ function and be able to swallow capsules or tablets. The study also considers lifestyle factors such as postmenopausal status in females, achieved naturally, surgically, or through ovarian function suppression. The trial includes a vulnerable population, ensuring comprehensive representation in the study.

The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled, Phase III study aimed at evaluating the efficacy of **abemaciclib** in combination with **fulvestrant** compared to placebo plus fulvestrant in participants with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic **breast cancer**. The trial will involve participants who have shown disease progression following treatment with a CDK4/6 inhibitor and endocrine therapy. The primary endpoint of the study is progression-free survival (PFS).

The trial is expected to last until February 2026, with recruitment having commenced in March 2022. Participants will be involved in the study for a maximum treatment period of 36 months. The study will include several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as postmenopausal status, adequate organ function, and the ability to swallow tablets; regular follow-up visits to monitor treatment response and safety; and an end-of-study visit to assess final outcomes. Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent.

Inclusion criteria require participants to have a diagnosis of HR+, HER2- locally advanced or metastatic breast cancer, with evidence of disease progression on prior therapies. Exclusion criteria are not specified in the provided data. The trial will utilize a combination of intramuscular administration of fulvestrant and oral administration of abemaciclib or placebo. The study is not categorized as low intervention and involves investigational medicinal products, with specific packaging and labeling for clinical trial use.

The clinical trial involves the administration of **fulvestrant**, a chemical substance, as an experimental medication. Fulvestrant is provided in a specific pharmaceutical form identified as PHF00231MIG. The medication is administered via the **intramuscular** route. The maximum daily dose of fulvestrant is 500 mg, with a total maximum dose of 20.5 g over the treatment period. The treatment duration is set for a maximum of 36 months. Clinical trial-specific packaging and labeling may be utilized for this medication.

In addition to fulvestrant, the trial includes a **placebo** designed to match abemaciclib. The placebo does not contain any active substance and is used to maintain the double-blind nature of the study. The pharmaceutical form and route of administration for the placebo are not specified in the trial data.

The trial also involves the administration of **abemaciclib**, marketed under the name Verzenios, in the form of 50 mg film-coated tablets. Abemaciclib is a chemical substance administered orally. The maximum daily dose is 300 mg, with a total maximum dose of 328.5 g over the treatment period. The treatment duration for abemaciclib is also set for a maximum of 36 months. The clinical trial utilizes different primary packaging, specifically bottles, than those authorized for marketing, along with trial-specific packaging and labeling.

The efficacy of the investigational treatment in this clinical trial will be assessed primarily through the measurement of **Progression-Free Survival (PFS)**. This endpoint is defined as the duration from the start of treatment until the disease progresses or the patient passes away from any cause. The trial is designed to compare the efficacy of the combination of **abemaciclib** and **fulvestrant** against a placebo plus fulvestrant in participants with HR+, HER2-, advanced or metastatic breast cancer who have shown progression following treatment with a CDK4/6 inhibitor and endocrine therapy.

The trial will employ a randomized, double-blind, placebo-controlled, Phase 3 design to ensure the reliability and validity of the results. Participants will be monitored for disease progression using radiologic assessments, which will be conducted at specified intervals throughout the study period. The data collected will be analyzed to determine the efficacy of the treatment regimen in extending the time patients remain free from disease progression compared to the control group. The study is expected to conclude by February 2026, with recruitment having started in March 2022.