Comparative Study of Short vs. Long Adjuvant Pembrolizumab and Nivolumab Therapy Post-Radical Surgery in Stage IIb-IV Cutaneous Malignant Melanoma

The primary objective of this study is to evaluate whether **adjuvant treatment** with immunotherapy for 6 months is as effective as 12 months in patients with stage IIb-c, III, and IV **cutaneous malignant melanoma**. This assessment is clinically relevant as it may determine the optimal duration of immunotherapy, potentially reducing treatment burden and associated side effects while maintaining efficacy.

Secondary objectives include assessing long-term distant metastatic free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) after 6 months compared to 12 months of immunotherapy. These measures are crucial for understanding the long-term benefits and risks associated with different durations of immunotherapy in high-risk melanoma patients.

The clinical trial involves participants diagnosed with **cutaneous malignant melanoma** at stages IIb-c, III, and IV. 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 are required to have undergone radical surgery for their condition and must have a WHO performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy of adjuvant immunotherapy in patients with stage IIb-c, III, and IV **cutaneous malignant melanoma**. The primary objective is to determine whether a 6-month treatment regimen is as effective as a 12-month regimen in terms of distant metastatic free survival (DMFS) and relapse-free survival (RFS). Secondary endpoints include overall survival (OS). The trial is expected to commence recruitment on September 2, 2024, and conclude by December 31, 2032, with an estimated duration of 8 years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as a WHO performance status of 0-1 and a history of radical surgery for the specified stages of melanoma. Following randomization, participants will receive either **pembrolizumab** or **nivolumab** via infusion, with the treatment period lasting up to 12 months. Regular follow-up visits will be scheduled to monitor the participants' health status, treatment adherence, and any adverse events. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

The expected length of participant involvement is up to 12 months, with conditions for early termination including significant adverse reactions, disease progression, or withdrawal of consent. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **KEYTRUDA** (pembrolizumab), a **concentrate for solution for infusion**. This experimental medication is provided in a concentration of 25 mg/mL and is administered via **infusion**. The maximum daily dose is 400 mg, with a total maximum dose of 3600 mg over a treatment period of up to 12 months. Pembrolizumab is a protein-based antineoplastic agent, specifically designed to target and modulate the immune system's response to cancer cells. The pharmaceutical form is a solution for infusion, ensuring precise delivery of the active substance. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Another experimental medication used in the trial is **OPDIVO** (nivolumab), also a **concentrate for solution for infusion**. It is available at a concentration of 10 mg/mL and is administered through **infusion**. The maximum daily dose for nivolumab is 480 mg, with a total maximum dose of 5760 mg over a 12-month treatment period. Like pembrolizumab, nivolumab is a protein-based antineoplastic agent, functioning as an immune checkpoint inhibitor to enhance the body's immune response against melanoma cells. The administration of nivolumab is carefully monitored to ensure participant compliance and to evaluate the efficacy of the treatment regimen.

Both medications are utilized in the context of a prospective randomized international multicenter study, aiming to compare the efficacy of short versus long adjuvant immunotherapy following radical surgery in patients with stage IIb-c, III, and IV cutaneous malignant melanoma. The trial's main objective is to determine if a 6-month treatment duration is as effective as a 12-month regimen. No non-experimental treatments, such as standard-of-care therapy or placebo, are specified in the trial protocol. The study strictly adheres to the outlined dosing schedules and administration routes to maintain the integrity of the trial results.

Efficacy in this clinical trial will be assessed using the primary endpoints of **distant metastatic free survival (DMFS)** and **relapse free survival (RFS)**. These parameters will be evaluated to determine the effectiveness of adjuvant immunotherapy administered for 6 months compared to 12 months in patients with stage IIb-c, III, and IV cutaneous malignant melanoma. The secondary endpoint for efficacy assessment is **overall survival (OS)**. The trial is designed to be a prospective, randomized, international multicenter study, focusing on the comparison of short versus long adjuvant immunotherapy following radical surgery for the specified stages of melanoma. The trial will utilize validated methods to measure and analyze these endpoints, ensuring robust and reliable data collection throughout the study period. The trial's main objective is to establish whether a shorter duration of immunotherapy is as effective as the standard longer duration in preventing disease progression and improving survival outcomes in the target patient population.