Continuation Study of Encorafenib, Binimetinib, and Ribociclib in Patients with Solid Tumors: Safety and Tolerability Assessment

The primary objective of this study is to monitor the **safety** and tolerability of the study interventions in participants with solid tumors. This is clinically relevant as it ensures that the therapeutic interventions, including Encorafenib and Binimetinib, are safe for continued use in patients, thereby minimizing potential adverse effects and optimizing patient outcomes.

The clinical trial involves a total of **21 participants** diagnosed with **solid tumors**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their ongoing clinical benefit from a parent study involving encorafenib/binimetinib, without experiencing significant adverse events related to the treatment. The trial includes individuals who are capable of providing informed consent and are willing to adhere to the study's scheduled visits and procedures. The population also includes vulnerable groups, ensuring a comprehensive assessment of the intervention's safety and tolerability. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed to monitor the safety and tolerability of the study interventions in participants with **solid tumors**. This trial follows a **randomized, double-blind, controlled** design, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to run until December 31, 2026, with recruitment having started on March 31, 2022. Participants will be involved in the study for a maximum treatment period of 60 days, with the possibility of early termination if adverse events (AEs) lead to permanent discontinuation of the study intervention or if serious adverse events (SAEs) occur.

The sequence of study visits includes an initial inclusion (screening) visit, where participants are assessed for eligibility based on criteria such as deriving clinical benefit from a parent study and the absence of intolerable adverse events. Follow-up visits are scheduled to monitor the participants' response to the treatment and to ensure compliance with the study protocol. The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted to evaluate the overall safety and efficacy of the interventions.

Participants are required to comply with all scheduled visits, treatment plans, and other study procedures as outlined in the protocol. The study involves the administration of various pharmaceutical forms, including tablets, film-coated tablets, hard capsules, and solutions for infusion, with the active substances being **ribociclib**, **binimetinib**, **encorafenib**, **vemurafenib**, and **cetuximab**. The trial's primary endpoints focus on AEs leading to permanent discontinuation and all SAEs, ensuring a comprehensive evaluation of the safety profile of the study interventions.

The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Ribociclib** is provided in two forms: as a **tablet** and as a **capsule**. The maximum daily dose for both forms is 600 mg, with a total maximum dose of 1,095,000 mg over a treatment period of 60 days. The administration route is oral, and the medication is of chemical origin. The active substance, ribociclib, is also known by the synonym LEE011.

**Mektovi** is administered as 15 mg **film-coated tablets** containing the active substance **binimetinib**. The maximum daily dose is 90 mg, with a total maximum dose of 164,250 mg over 60 days. The tablets are taken orally, and the active substance is of chemical origin, also referred to as MEK162.

**Braftovi** is available in two dosages: 50 mg and 75 mg **hard capsules**, both containing the active substance **encorafenib**. The maximum daily dose for both dosages is 450 mg, with a total maximum dose of 821,250 mg over the treatment period. The capsules are administered orally, and the active substance is of chemical origin.

**Zelboraf** is provided as 240 mg **film-coated tablets** with the active substance **vemurafenib**. The maximum daily dose is 1,920 mg, with a total maximum dose of 1,920 mg over 60 days. The administration route is oral, and the active substance is of chemical origin.

**Erbitux** is administered as a 5 mg/mL **solution for infusion** containing the active substance **cetuximab**. The maximum daily dose is 500 mg/m², with a total maximum dose of 60,000 mg/m² over the treatment period. The solution is administered via infusion, and the active substance is a protein of other origin.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. All medications are packaged and labeled according to study-specific requirements and country regulations.

The efficacy of the clinical trial will be assessed using specific primary endpoints. These endpoints include adverse events (AEs) leading to permanent discontinuation of the study intervention and all serious adverse events (SAEs). The evaluation of these endpoints will provide insights into the safety and tolerability of the study interventions, which are critical components of the trial's main objective. The trial is designed to monitor the safety and tolerability of the interventions, ensuring that participants continue to derive clinical benefit from the study treatments.