Efficacy and Safety Evaluation of Pembrolizumab in Advanced Progressive Adrenocortical Carcinoma: A Multicenter Phase 2 Open-Label Study

The primary objective of this multicentre, open-label phase 2 study is the **evaluation of the efficacy** of pembrolizumab in the treatment of advanced progressive **adrenocortical carcinoma**. This objective is clinically relevant as it aims to determine the therapeutic potential of pembrolizumab, a monoclonal antibody, in managing a challenging and aggressive form of cancer, potentially offering a new treatment avenue for patients with limited options.

Secondary objectives include:

• Assessment of the **safety** of pembrolizumab in the treatment of advanced, progressive adrenocortical cancer, which is crucial for understanding the risk-benefit profile of the therapy.
• Assessment of the impact of therapy on the patient's **quality of life**, providing insights into the broader implications of treatment beyond clinical efficacy.

The clinical trial focuses on evaluating the efficacy of pembrolizumab in the treatment of advanced progressive **adrenocortical carcinoma**. The study population includes both male and female participants, aged 18 and older, with a histopathologically confirmed diagnosis of adrenal cortex cancer. Participants are required to have a general health status assessed as less than 2 on the ECOG scale, indicating they are ambulatory and capable of all self-care but unable to carry out any work activities. The trial includes individuals with measurable disease and confirmed progression according to RECIST 1.1 criteria within the last six months, following at least one line of treatment with EDP or EDP-M. Adequate bone marrow and internal organ function are necessary, with specific laboratory parameters outlined for inclusion. Both men and women of reproductive age must adhere to double barrier contraception methods, with women also requiring a confirmed negative pregnancy test. The trial population selection criteria ensure a focus on individuals with advanced disease progression, although the total number of participants is not provided by the sponsor.

The clinical trial is designed to evaluate the efficacy and safety of **pembrolizumab** in the treatment of advanced, progressive **adrenocortical carcinoma**. This is a multicenter, open-label, phase 2 study. The trial will involve adult participants who have histopathologically confirmed adrenal cortex cancer and meet specific inclusion criteria, such as a general condition assessed according to the ECOG scale of less than 2 and measurable disease according to RECIST 1.1. Participants must have confirmed disease progression within the last six months and adequate function of bone marrow and internal organs. The study will assess primary endpoints including Objective Response Rate (ORR), Progression-Free Survival (PFS), Duration of Response (DoR), and Overall Survival (OS). Secondary endpoints will include quality of life assessed by the QLQ-C30 questionnaire and the number of adverse events and serious adverse events related and unrelated to treatment according to CTCAE.

The trial is expected to start recruitment on January 30, 2023, and is estimated to conclude by December 1, 2025. Participants will receive **pembrolizumab** administered via intravenous use, with a maximum daily dose of 200 mg and a total dose not exceeding 3400 mg over a maximum treatment period of 48 weeks. The study will include an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor treatment response and safety. The end-of-study visit will occur after the completion of the treatment period or upon early termination. Participants may be withdrawn from the study if they experience unacceptable toxicity, disease progression, or withdraw consent. The expected length of participant involvement is up to 48 weeks, depending on individual response and tolerability.

The clinical trial involves the administration of **pembrolizumab**, an experimental medication, to evaluate its efficacy and safety in the treatment of advanced, progressive adrenocortical carcinoma. **Pembrolizumab** is provided in the pharmaceutical form of a concentrate for solution for injection. The active substance, **pembrolizumab**, is a protein of other origin. The medication is administered via the **intravenous route**. The dosing regimen includes a maximum daily dose of 200 mg, with a total maximum dose of 3400 mg over the course of the treatment. The maximum treatment period is 48 weeks. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of **pembrolizumab** to assess its therapeutic potential in the specified patient population. Participants are closely monitored for any adverse effects and efficacy outcomes, with data collected at regular intervals to evaluate the primary and secondary objectives of the trial.

The efficacy of pembrolizumab in the treatment of advanced progressive adrenocortical carcinoma will be assessed through a multicentre, open-label phase 2 clinical trial. The primary endpoints for evaluating efficacy include the **Objective Response Rate (ORR)**, **Progression-Free Survival (PFS)**, **Duration of Response (DoR)**, and **Overall Survival (OS)**. These parameters will provide a comprehensive assessment of the treatment's impact on disease progression and patient survival.

Secondary endpoints will focus on the quality of life, assessed using the QLQ-C30 questionnaire, and the number of Adverse Events and Serious Adverse Events (AEs and SAEs) related and unrelated to treatment, as classified by the Common Terminology Criteria for Adverse Events (CTCAE). These secondary measures will offer additional insights into the treatment's safety profile and its effect on patients' well-being.