Evaluation of Belvarafenib Monotherapy and Combination Therapy with Cobimetinib and Nivolumab in NRAS-Mutant Advanced Cutaneous Melanoma Patients

The primary objective of this study is to evaluate the **safety**, pharmacokinetics, and activity of **Belvarafenib** as a single agent and in combination with either **Cobimetinib** or Cobimetinib plus **Nivolumab** in patients with **NRAS-mutant advanced cutaneous melanoma**. This is clinically relevant as NRAS mutations are associated with a poor prognosis in melanoma, and effective treatment options are limited. Understanding the safety profile and pharmacokinetics of these combinations could provide valuable insights into potential therapeutic strategies for this patient population.

The clinical trial involves a total of **49 participants** diagnosed with **NRAS-mutant advanced cutaneous melanoma**. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected to include a vulnerable population, although specific inclusion or exclusion criteria were not provided by the sponsor. The general health status of the participants is not detailed, nor are any lifestyle considerations such as diet, physical activity, or habits. The trial aims to gather data from a diverse group, reflecting a broad spectrum of individuals affected by this specific type of melanoma.

The clinical trial is designed to evaluate the **safety**, pharmacokinetics, and activity of Belvarafenib as a single agent and in combination with either Cobimetinib or Cobimetinib plus Nivolumab in patients with **NRAS-mutant advanced cutaneous melanoma**. This study is a Phase 3, randomized, double-blind, controlled trial. The estimated recruitment start date was May 14, 2021, and the trial is expected to conclude by November 25, 2025. Participants will be randomly assigned to different treatment groups to ensure unbiased results. The trial will maintain a double-blind design, meaning neither the participants nor the investigators will know which treatment the participants are receiving, to prevent bias in the assessment of outcomes.

The sequence of study visits begins with an inclusion (screening) visit, where potential participants are assessed for eligibility based on predefined criteria. Following successful screening, participants will undergo baseline assessments before the initiation of treatment. Regular follow-up visits will be scheduled to monitor the participants' health, treatment adherence, and any adverse events. These visits will also include assessments of the drug's pharmacokinetics and activity. The end-of-study visit will occur after the completion of the treatment period, where final evaluations will be conducted to assess the overall outcomes and any long-term effects of the treatment.

The expected length of participant involvement in the study will vary depending on the treatment arm and individual response to the therapy. Participants may be withdrawn from the study early if they experience significant adverse effects, if the disease progresses despite treatment, or if they choose to withdraw consent. The study is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of an **experimental medication**. However, specific details regarding the name, pharmaceutical form, dosage, route, and frequency of administration of the experimental medication are not provided in the available data. The trial documentation does not specify whether the medication is a **paediatric formulation** or if it is classified as an **orphan drug**. Additionally, there is no information on the maximum daily dose, total dose, or treatment period for the experimental medication.

In addition to the experimental medication, the trial may include the use of **non-experimental treatments** such as standard-of-care therapy, placebo, or comparator treatments. However, the data does not provide explicit details about these treatments. Information regarding the administration, dosing schedules, and participant compliance monitoring for these non-experimental treatments is also not available.

The clinical trial is a Phase 3 study, with an estimated recruitment start date of May 14, 2021, and an estimated end date of November 25, 2025. Efficacy will be assessed through a structured evaluation process, although specific parameters or endpoints for efficacy assessment are not detailed in the available data. The trial will follow a systematic approach to measure, collect, and analyze efficacy data, adhering to the standards expected in a Phase 3 clinical trial. The methods and schedule for these assessments, as well as any specific tools or instruments to be used, are not specified in the provided information. The trial is categorized under trial category 1, with a trial category ID of 65102, indicating its classification within the clinical trial framework.