Phase 3 Randomized Double‑Blind Trial of Adjuvant MK‑7684A (Vibostolimab + Pembrolizumab) versus Pembrolizumab in High‑Risk Stage II‑IV Melanoma

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 Stage II-IV melanoma. This objective 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 patient outcomes.

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.
• Assessing MK-7684A compared to pembrolizumab regarding the mean change from baseline in global health status/quality of life (QoL), physical functioning, and role functioning using the EORTC QLQ-C30.

The clinical trial involves a total of **1133 participants** diagnosed with **melanoma**, specifically targeting individuals with surgically resected and histologically or pathologically confirmed Stage IIB, IIC, III, or IV cutaneous melanoma, as per the American Joint Committee on Cancer (AJCC) eighth edition guidelines. The study population includes both male and female subjects, encompassing a diverse age range. Participants were selected based on specific criteria, including the absence of prior systemic therapy for melanoma beyond surgical resection and a maximum of 12 weeks between final surgical resection and randomization. The trial also includes individuals with well-controlled HIV on anti-retroviral therapy. The population is characterized by a mix of general health statuses, and the trial does not specify any particular lifestyle considerations such as diet or physical activity. The inclusion of a vulnerable population is noted, ensuring a comprehensive evaluation of the trial's objectives.

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 **vibostolimab** and **pembrolizumab**) compared to pembrolizumab alone in participants with high-risk Stage II-IV **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 from June 2023 to June 2025, with a maximum treatment period of 12 months for each participant.

Participants will be randomly assigned to receive either MK-7684A or pembrolizumab, both administered via **intravenous infusion**. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and adverse events, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to have a surgically resected and confirmed diagnosis of Stage IIB, IIC, III, or IV cutaneous melanoma, with no prior systemic therapy beyond surgical resection. Participants must also have had no more than 12 weeks between their final surgical resection and randomization.

The expected length of participant involvement is up to 12 months, with conditions for early termination including significant adverse events or withdrawal of consent. The study 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 melanoma.

The clinical trial involves the administration of two experimental medications. The first medication is **KEYTRUDA**, a **concentrate for solution for infusion** containing the active substance **pembrolizumab**. This medication is provided by Merck Sharp & Dohme BV and is administered via **intravenous infusion**. The dosage is set at a maximum of 200 mg per day, with a total maximum dose of 3400 mg over a treatment period of up to 12 months. Pembrolizumab is a protein-based therapeutic agent, specifically a monoclonal antibody, and is utilized in this study as a comparator treatment.

The second experimental medication is **MK-7684A**, a **solution for infusion** that combines the active substances **pembrolizumab** and **vibostolimab**. This formulation is provided by Merck & Co. Inc. and is also administered via **intravenous infusion**. The maximum daily dosage for MK-7684A is 400 mg, with a total maximum dose of 6800 mg over a 12-month treatment period. Vibostolimab, like pembrolizumab, is a protein-based therapeutic agent, specifically a humanized monoclonal antibody targeting the TIGIT receptor. This medication serves as the test treatment in the study.

Both treatments are administered in a controlled clinical setting, with participant compliance monitored throughout the study duration. The trial aims to compare the efficacy of MK-7684A against pembrolizumab in terms of recurrence-free survival (RFS) in participants with high-risk Stage II-IV melanoma. No non-experimental treatments, such as standard-of-care therapy or placebo, are utilized in this study.

Efficacy in this clinical trial will be assessed primarily through **Recurrence-Free Survival (RFS)**, which serves as the primary endpoint. Secondary endpoints include **Distant Metastasis-Free Survival (DMFS)**, **Overall Survival (OS)**, and various 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. Additionally, the number of participants experiencing at least one adverse event (AE) and those who discontinue study treatment due to an AE will be evaluated.

The trial involves a Phase 3, randomized, double-blind, active-comparator-controlled design, comparing the efficacy of MK-7684A (a combination of **Vibostolimab** and **Pembrolizumab**) versus Pembrolizumab alone in participants with high-risk Stage II-IV melanoma. The efficacy parameters will be measured and collected at specified intervals throughout the study duration, with the final analysis conducted at the end of the treatment period. The study is designed to ensure rigorous assessment of the treatment's impact on the defined endpoints, providing comprehensive data on the comparative efficacy of the investigational product.