14 Participants Needed

BRAF-MEK Inhibitor Therapy for Melanoma

Age: 18+
Sex: Any
Trial Phase: Phase < 1
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This pilot early phase I trial studies how well encorafenib, binimetinib, and nivolumab work in treating patients with BRAF mutant stage IIIC-IV melanoma. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with nivolumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving encorafenib, binimetinib, and nivolumab may kill more tumor cells.

Do I need to stop my current medications to join the trial?

The trial allows patients to continue taking non-biologic disease modifying agents and low-dose corticosteroids (up to 10 mg of prednisone daily). However, hormonal contraceptives should not be used during the trial.

What safety information is available for BRAF-MEK inhibitor therapy in humans?

Encorafenib and binimetinib, used together for treating melanoma, can cause side effects like inflammatory colitis (inflammation of the colon) and skin issues. However, they have shown an acceptable safety profile in some studies, with fewer cases of fever and sensitivity to sunlight compared to other similar treatments.12345

How is the drug combination of Encorafenib, Binimetinib, and Nivolumab unique for treating melanoma?

This drug combination is unique because it targets specific mutations (BRAF V600E/K) in melanoma using a combination of BRAF and MEK inhibitors (Encorafenib and Binimetinib), which have shown to improve survival rates, and it includes Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells.24678

What data supports the effectiveness of the drug combination Encorafenib and Binimetinib for treating melanoma?

Research shows that the combination of Encorafenib and Binimetinib improves survival and quality of life in patients with BRAF-mutant melanoma, compared to other treatments like vemurafenib. This combination is effective in targeting specific mutations found in about 40% of metastatic melanoma cases.24689

Who Is on the Research Team?

Zeynep Eroglu | Moffitt

Zeynep Eroglu

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

Adults with advanced BRAF mutant melanoma (stage IIIC-IV) who have measurable disease, good organ function, and an ECOG performance status of ≤2. They must not be pregnant or nursing, agree to use non-hormonal contraception for 6 months post-treatment, and haven't had certain prior treatments like BRAF/MEK inhibitors in the metastatic setting.

Inclusion Criteria

You need to have a certain amount of a specific type of DNA in your blood when you start the study.
I will use non-hormonal birth control during and for 6 months after treatment.
Your creatinine level is less than or equal to 2 times the upper limit of normal at the study site.
See 12 more

Exclusion Criteria

I have had cancer before, but it's under control and I'm not currently on cancer treatment.
I do not have any serious ongoing illnesses and my heart is classified as class 2B or better.
I have HIV, am on effective treatment, and my last viral load was undetectable.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 450 mg Encorafenib daily, 45 mg Binimetinib twice daily, and 240 mg Nivolumab IV every 2 weeks

8 weeks
4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for time to treatment failure and tumor response

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Encorafenib; Binimetinib
  • Nivolumab
Trial Overview The trial is testing a combination of encorafenib and binimetinib—drugs that block enzymes promoting tumor growth—with nivolumab, which may help the immune system fight cancer. The goal is to see if this trio can effectively kill more melanoma cells.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A: BRAF-MEK Inhibitor TherapyExperimental Treatment3 Interventions
Participants will receive 450 mg Encorafenib daily, along with 45 mg Binimetinib twice daily and 240 mg Nivolumab IV every 2 weeks.
Group II: Arm BActive Control1 Intervention
Participants will receive 240 mg Nivolumab IV every 2 weeks

Find a Clinic Near You

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials
576
Recruited
145,000+

Published Research Related to This Trial

Encorafenib and binimetinib are effective small-molecule inhibitors that target the BRAF and MEK proteins in the MAPK signaling pathway, significantly improving overall and progression-free survival in patients with metastatic melanoma harboring BRAF V600 mutations.
This combination therapy received FDA approval in June 2018 specifically for treating melanoma with BRAF V600E/K mutations, highlighting its clinical utility and relevance in modern cancer treatment.
Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma.Rose, AAN.[2019]
In a phase 3 study involving 577 patients with advanced BRAFV600-mutant melanoma, the combination of encorafenib and binimetinib significantly improved median progression-free survival to 14.9 months compared to 7.3 months with vemurafenib, indicating greater efficacy of the combination therapy.
The encorafenib plus binimetinib treatment showed a better tolerability profile with fewer severe adverse events compared to encorafenib or vemurafenib alone, suggesting it could be a safer treatment option for patients.
Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.Dummer, R., Ascierto, PA., Gogas, HJ., et al.[2022]
In the COLUMBUS study involving 577 patients with advanced BRAF-mutant melanoma, the combination treatment of encorafenib plus binimetinib significantly improved health-related quality of life (HRQoL) scores compared to vemurafenib, indicating a meaningful enhancement in patients' perceived health status.
Patients receiving the combination therapy also experienced a delay in deterioration of quality of life, suggesting that this treatment not only improves survival but also helps maintain a better quality of life during treatment.
Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS).Gogas, H., Dummer, R., Ascierto, PA., et al.[2021]

Citations

Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma. [2019]
Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. [2022]
Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS). [2021]
Preclinical discovery and clinical development of encorafenib for the treatment of melanoma. [2021]
The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma. [2019]
Severe Inflammatory Colitis Related to Encorafenib and Binimetinib following Immune Checkpoint Inhibitor Therapy. [2022]
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. [2023]
[Long-term efficacy of encorafenib plus binimetinib combined treatment: case report.] [2021]
The discovery and development of binimetinib for the treatment of melanoma. [2021]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security