Phase 2 Evaluation of Abemaciclib, Irinotecan, and Temozolomide in Relapsed or Refractory Ewing's Sarcoma

The primary objective of this Phase 2 study is to evaluate the clinical benefit of adding **abemaciclib** to the chemotherapy regimen of **irinotecan** and **temozolomide** in patients with relapsed or refractory **Ewing's sarcoma**. This objective is clinically relevant as it aims to determine whether the addition of abemaciclib can enhance the therapeutic efficacy in a patient population that has limited treatment options due to the recurrence or resistance of the disease. The study does not list any secondary objectives.

The clinical trial involves a total of **11 participants** diagnosed with **Ewing's sarcoma** or Ewing's sarcoma-like tumors. The study population includes both male and female subjects, aged between **1 to less than 40 years**, with a body weight of at least **10 kg**. Participants were selected based on confirmed radiological progression, refractory disease, or recurrence following prior treatment, and must have at least one measurable or evaluable lesion. The trial includes individuals with adequate hematologic and organ function, as well as those who have discontinued previous cancer treatments and recovered from acute effects. Participants must be able to swallow or have a gastric/nasogastric tube, with specific requirements for those in the European Union to swallow intact capsules. The study does not specify particular lifestyle considerations such as diet or physical activity. The trial population includes vulnerable groups, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographics.

The clinical trial is a **randomized**, open-label Phase 2 study designed to evaluate the efficacy of **abemaciclib** in combination with **irinotecan** and **temozolomide** in participants with relapsed or refractory **Ewing's sarcoma**. The primary objective is to assess the benefit of adding abemaciclib to the chemotherapy regimen for this condition. The trial is expected to run from October 2022 to April 2026, with the primary endpoint being progression-free survival as determined by a blinded independent review committee using RECIST 1.1 criteria.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, body weight, and adequate organ function. The trial includes multiple follow-up visits to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any long-term effects of the treatment.

The expected duration of participant involvement is approximately 31 days, with conditions for early termination including significant adverse reactions or disease progression. Participants must meet specific inclusion criteria, such as a confirmed diagnosis of Ewing's sarcoma, adequate performance status, and the ability to swallow medication. Exclusion criteria are not specified in the provided data. The trial involves oral administration of abemaciclib and temozolomide, while irinotecan is administered intravenously. The study aims to provide valuable insights into the potential benefits of this combination therapy for Ewing's sarcoma.

The clinical trial involves the administration of **Verzenios** 50 mg film-coated tablets, which contain the active substance **abemaciclib**. This medication is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 200 mg, with a total maximum dose of 189,000 mg over a treatment period of 31 days. The tablets are specifically packaged and labeled for the clinical trial, differing from the standard marketing authorization packaging. Abemaciclib is of chemical origin and classified as an antineoplastic agent.

**Temozolomide** is another treatment used in the study, provided in a pharmaceutical form denoted as PHF00005MIG. It is also of chemical origin and classified as an antineoplastic agent. Temozolomide is administered orally, with a maximum daily dose of 100 mg/m² and a total maximum dose of 45,000 mg over the same 31-day treatment period. The medication is re-labeled and re-packaged specifically for the clinical trial.

**Irinotecan hydrochloride** is included as a comparator treatment in the trial. It is provided in a pharmaceutical form identified as PHF00230MIG and is administered intravenously. The maximum daily dose is 50 mg/m², with a total maximum dose of 22,500 mg over the 31-day treatment period. Like temozolomide, irinotecan hydrochloride is re-packaged and re-labeled for the purposes of the clinical trial. It is also of chemical origin and classified as an antineoplastic agent.

Additionally, **Abemaciclib** is provided in two other forms: as a standard tablet and as granules, both of which are administered orally. The granules are specifically formulated for pediatric use. The maximum daily dose for both forms is 200 mg, with a total maximum dose of 189,000 mg over the 31-day treatment period. These forms are also of chemical origin and classified as antineoplastic agents, with specific packaging and labeling for the clinical trial.

The efficacy of the clinical trial will be assessed primarily through **Progression Free Survival** (PFS) as determined by a blinded independent review committee. This evaluation will utilize the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). The trial is designed to measure the benefit of adding **abemaciclib** to chemotherapy regimens consisting of **irinotecan** and **temozolomide** in participants with relapsed or refractory Ewing's sarcoma. The primary endpoint, PFS, will provide insights into the duration during which the disease does not progress, offering a critical measure of the treatment's efficacy.