A Phase 3, Randomized, Double-blind, Active-Comparator-Controlled Clinical Study of Adjuvant MK-7684A (Vibostolimab with Pembrolizumab) Versus Adjuvant Pembrolizumab in Participants with High-risk Stage II-IV Melanoma (KEYVIBE-010)

The primary objective of this Phase 3 clinical study is to compare **MK-7684A** (a combination of vibostolimab and pembrolizumab) to pembrolizumab alone with respect to recurrence-free survival (RFS) in participants with high-risk resected melanoma. This comparison is clinically relevant as it aims to determine the efficacy of the combination therapy in preventing melanoma recurrence, which is critical for improving long-term outcomes in patients with high-risk stages of the disease.

Secondary objectives include:

• Comparing MK-7684A to pembrolizumab with respect to distant metastasis-free survival (DMFS).
• Comparing MK-7684A to pembrolizumab with respect to overall survival (OS).
• Evaluating the safety and tolerability of MK-7684A and pembrolizumab.
• Comparing MK-7684A to pembrolizumab with respect to mean change from baseline in global health status/quality of life (QoL), physical functioning, and role functioning using the EORTC QLQ-C30.

These secondary objectives are essential for assessing the broader impact of the treatment on patient health and quality of life, as well as ensuring the safety of the therapeutic regimen.

The clinical trial involves a total of **1296 participants** diagnosed with **high-risk resected melanoma**. The study population includes both male and female subjects, encompassing a broad **age range** that includes young adults, adults, and older adults. Participants were selected based on specific criteria, including a surgically resected and histologically or pathologically confirmed diagnosis of Stage IIB, IIC, III, or IV cutaneous melanoma, as per the American Joint Committee on Cancer (AJCC) eighth edition guidelines. The trial includes individuals who have not received any prior systemic therapy for melanoma beyond surgical resection and have had no more than 12 weeks between final surgical resection and randomization. Additionally, **HIV-infected participants** are included, provided their condition is well controlled on anti-retroviral therapy (ART). The trial population is diverse, including vulnerable populations, and is designed to compare MK-7684A to pembrolizumab with respect to recurrence-free survival (RFS).

The clinical trial is a **Phase 3**, randomized, double-blind, active-comparator-controlled study designed to evaluate the efficacy and safety of MK-7684A (a combination of **pembrolizumab** and **vibostolimab**) compared to pembrolizumab alone in participants with high-risk resected melanoma. The primary objective is to assess recurrence-free survival (RFS), with secondary endpoints including distant metastasis-free survival (DMFS), overall survival (OS), and quality of life measures. The trial is expected to run until March 31, 2031, with recruitment having commenced on February 22, 2023.

Participants will be randomly assigned to receive either the investigational product MK-7684A or the comparator pembrolizumab, both administered via **intravenous infusion**. The maximum treatment period for each participant is 12 months. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. Participants are required to have a surgically resected and histologically confirmed diagnosis of Stage IIB, IIC, III, or IV cutaneous melanoma, with no prior systemic therapy beyond surgical resection.

The expected duration of participant involvement is approximately 12 months, with conditions for early termination including the occurrence of unacceptable adverse events or disease progression. The trial aims to provide comprehensive data on the comparative effectiveness of the investigational combination therapy versus the standard treatment, contributing valuable insights into the management of high-risk resected melanoma.

The clinical trial involves the administration of two experimental medications. The first medication is **KEYTRUDA** (pembrolizumab), a **concentrate for solution for infusion**. It is administered via **intravenous infusion**. The pharmaceutical form is a solution for infusion, with a concentration of 25 mg/mL. The maximum daily dose is 200 mg, and the total maximum dose over the treatment period is 3400 mg. The treatment period extends up to 12 months. Pembrolizumab is a protein-based therapeutic agent, specifically a monoclonal antibody, and is not formulated for pediatric use. The medication is manufactured by Merck Sharp & Dohme BV and is authorized for use in the European Union.

The second experimental medication is a combination product, MK-7684A, which contains **pembrolizumab** and **vibostolimab**. This medication is also in the form of a **solution for infusion** and is administered via **intravenous infusion**. The maximum daily dose for this combination is 400 mg, with a total maximum dose of 6800 mg over a 12-month treatment period. Vibostolimab is a humanized monoclonal antibody targeting the T-cell immunoreceptor with Ig and ITIM domains (TIGIT). This combination product is manufactured by Merck & Co. Inc. and is not intended for pediatric use. Both pembrolizumab and vibostolimab are protein-based therapeutic agents.

In this study, the comparator treatment is pembrolizumab alone, while the test treatment is the combination of pembrolizumab and vibostolimab. The trial aims to compare the efficacy of MK-7684A to pembrolizumab in terms of recurrence-free survival (RFS) in participants with high-risk Stage II-IV melanoma. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed primarily through the measurement of **Recurrence-Free Survival (RFS)**. This endpoint will evaluate the time from randomization to the first occurrence of melanoma recurrence or death from any cause. Secondary efficacy endpoints include **Distant Metastasis-Free Survival (DMFS)**, **Overall Survival (OS)**, and patient-reported outcomes such as changes from baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) scores, specifically focusing on Global Health Status/Quality of Life, Physical Functioning, and Role Functioning.

The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the trial. The EORTC QLQ-C30 will be utilized as a validated tool to assess patient-reported outcomes, providing insights into the participants' quality of life and functional status. The trial is designed to compare the efficacy of MK-7684A (Vibostolimab with Pembrolizumab) versus Pembrolizumab alone in participants with high-risk Stage II-IV melanoma. The study will follow a randomized, double-blind, active-comparator-controlled design to ensure robust and unbiased results.