112 Participants Needed

Encorafenib/Binimetinib/Nivolumab vs Ipilimumab/Nivolumab for Melanoma

Recruiting at 333 trial locations
CM
DS
Overseen ByDana Sparks
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for melanoma that has spread to the brain. It compares two approaches: one combines encorafenib (a BRAF inhibitor), binimetinib (a MEK inhibitor), and nivolumab (an immunotherapy drug), while the other uses nivolumab and ipilimumab (both immunotherapy drugs). The goal is to determine which treatment better shrinks and controls brain tumors. It suits individuals with BRAF-V600 mutant melanoma that has metastasized to the brain and who have not received prior systemic therapy for their metastatic disease. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have a serious active infection requiring treatment, and you must not be planning to use hormonal contraceptives. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of encorafenib, binimetinib, and nivolumab is generally well-tolerated. In previous studies with patients who have BRAF-mutant melanoma, many continued treatment without major issues, though some experienced side effects. These studies highlighted that while the treatment improved survival rates, monitoring side effects was important.

In contrast, the combination of nivolumab and ipilimumab has been studied for a longer period. A large study found that about half of the patients experienced severe side effects, such as tiredness or skin problems. Despite this, many patients continued with the treatment due to its good long-term results.

Both treatments have shown benefits, but side effects can occur. Participants in a trial will have their health closely monitored by doctors to manage any side effects that might arise.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial for melanoma because they offer potential new combinations and approaches that differ from standard therapies. The combination of encorafenib, binimetinib, and nivolumab is novel because it integrates targeted therapy with immunotherapy. Encorafenib and binimetinib specifically target the BRAF/MEK pathway, which is often mutated in melanoma, while nivolumab enhances the immune response against cancer cells. Meanwhile, the nivolumab and ipilimumab combination, already a standard practice, is being re-evaluated to see if it can be optimized further. These approaches could lead to more effective and personalized treatment options for melanoma patients.

What evidence suggests that this trial's treatments could be effective for melanoma with brain metastases?

In this trial, participants will receive one of two treatment combinations. Research has shown that the combination of encorafenib, binimetinib, and nivolumab, one of the treatment arms in this trial, can benefit patients with a specific type of melanoma (BRAF V600-mutant) that has spread to the brain. In one study, 36% of patients treated with these drugs were still alive after 18 months. Previous studies also found positive results for patients with melanoma that spread to the brain when treated with encorafenib and binimetinib.

The other treatment arm involves the combination of ipilimumab and nivolumab, which has demonstrated impressive long-term results. Specifically, after 10 years, 96% of patients who were free of disease progression at 3 years were still alive. Both treatment combinations in this trial show promise for managing melanoma that has spread to the brain.24567

Who Is on the Research Team?

ZE

Zeynep Eroglu

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with BRAF-V600 mutant melanoma that has spread to the brain. They must be able to take pills, have a certain level of physical fitness (Zubrod status <=2), and their major organs need to function within specific limits. People with HIV can join if they're on effective therapy. Those who've had other cancers may qualify if it doesn't affect this study's safety or results.

Inclusion Criteria

Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
I had hepatitis C but have been treated and cured.
I have HIV, am on effective treatment, and my recent tests show no detectable virus.
See 21 more

Exclusion Criteria

I have not had radiation therapy in the last 7 days.
I am using effective birth control.
I do not have a serious infection needing treatment according to my doctor.
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either encorafenib, binimetinib, and nivolumab or nivolumab and ipilimumab. Treatment cycles repeat every 21-28 days depending on the arm, in the absence of disease progression or unacceptable toxicity.

Varies by arm, up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 6 months for 2 years, then annually until 3 years after randomization.

3 years

What Are the Treatments Tested in This Trial?

Interventions

  • Encorafenib, Binimetinib
  • Ipilimumab, Nivolumab
Trial Overview The trial compares two treatments for melanoma in the brain: one group receives Encorafenib + Binimetinib + Nivolumab, while the other gets Ipilimumab + Nivolumab. The goal is to see which combination better controls or shrinks brain metastases from melanoma.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Arm II (nivolumab, ipilimumab)Experimental Treatment2 Interventions
Group II: Arm I (encorafenib, binimetinib, nivolumab)Experimental Treatment3 Interventions

Encorafenib, Binimetinib is already approved in United States, European Union for the following indications:

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Approved in United States as Braftovi and Mektovi for:
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Approved in European Union as Braftovi and Mektovi for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials
403
Recruited
267,000+

Southwest Oncology Group

Lead Sponsor

Trials
389
Recruited
260,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

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]
In a 5-year study of patients with advanced BRAF V600-mutant melanoma, those treated with the combination of encorafenib and binimetinib (COMBO group) had a longer duration of survival without disease progression compared to those receiving either encorafenib alone or vemurafenib.
The combination treatment also resulted in fewer patients needing additional anticancer therapies after treatment, and while side effects were similar across all groups, they decreased over time for the COMBO group.
COLUMBUS 5-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF.Dummer, R., Flaherty, KT., Robert, C., et al.[2023]
In the COLUMBUS trial involving 577 patients with BRAFV600-mutant melanoma, the combination of encorafenib and binimetinib significantly improved overall survival (33.6 months) compared to vemurafenib (16.9 months), indicating a strong efficacy of the combination therapy.
The safety profile of encorafenib plus binimetinib was acceptable, with common grade 3 or 4 adverse events being manageable, suggesting that this combination therapy is a promising treatment option for patients with this type of melanoma.
Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial.Dummer, R., Ascierto, PA., Gogas, HJ., et al.[2019]

Citations

Encorafenib/Binimetinib/Nivolumab Improves PFS in ...Notably, the 18-month overall survival (OS) rates were 36% (95% CI, 13%-60%) in the encorafenib plus binimetinib and nivolumab group vs 37% (95% ...
Efficacy of encorafenib plus binimetinib in patients with ...Encorafenib/binimetinib has clinical activity in real-world melanoma patients with BMs. Their prognosis is determined by the presence of symptomatic BMs, age, ...
A randomized phase 2 trial of encorafenib + binimetinib ...With enco/bini/nivo, 69% of pts had grade 3-4 toxicity, and with ipi/nivo, 75% had grade 3-5 toxicity, with one death due to cardiac arrest.
COLUMBUS 5-Year Update - PubMed CentralIn conclusion, 35% of patients with unresectable or metastatic BRAF V600–mutant melanoma treated with encorafenib plus binimetinib in COLUMBUS were alive after ...
Combination of encorafenib and binimetinib followed by ...Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol. 2022; 40:127-137.
Study Details | NCT04655157 | Safety and Efficacy in ...Patients with unresectable or metastatic BRAF-mutant melanoma high-risk patients will be given 450 mg orally (PO) daily (QD) plus binimetinib 45 mg PO twice ...
COLUMBUS 7-year update: A randomized, open-label ...Median melanoma-specific survival (95 % CI) was 36.8 months (27.7–51.5 months) in the encorafenib plus binimetinib arm and 19.3 months (14.8–25.9 months) in the ...
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