Encorafenib + Binimetinib for Melanoma

(COLUMBUS-AD Trial)

Recruiting at 179 trial locations

Overseen By Isabelle Klauck, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pierre Fabre Medicament

Disqualifiers: Pregnancy, Metastases, Cardiovascular diseases, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

815 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on anticoagulant therapy, you may continue as long as your blood tests are within the therapeutic range.

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

The combination of Encorafenib and Binimetinib has shown to improve overall survival in patients with advanced BRAF mutation-positive melanoma, achieving a median overall survival of 33.6 months, which is longer than other similar drug combinations. Additionally, this combination may have fewer side effects like fever and sensitivity to sunlight, making it a potentially better option for patients. ^{1 2 3 4 5}

Is the combination of Encorafenib and Binimetinib safe for humans?

The combination of Encorafenib and Binimetinib has shown an acceptable safety profile in patients with certain types of melanoma and non-small-cell lung cancer, although some patients may experience side effects like visual symptoms. ^{2 6 7 8 9}

How is the drug combination of encorafenib and binimetinib unique for treating melanoma?

The drug combination of encorafenib and binimetinib is unique for treating melanoma because it targets specific mutations in the BRAF gene, offering improved overall survival and progression-free survival compared to other treatments. It also has fewer side effects like fever and skin sensitivity, making it more tolerable for patients. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of the Columbus-AD study is to evaluate the efficacy and safety of 12 months of encorafenib in combination with binimetinib in adjuvant setting of BRAF V600E/K mutant stage IIB/C melanoma versus the current standard of care (surveillance).

Research Team

Alexander C.J. van AKKOOI, MD, PhD

Principal Investigator

European Organisation for Research and Treatment of Cancer - EORTC

Eligibility Criteria

Adults over 18 with high-risk Stage II melanoma that has a BRAF mutation, who've had surgery recently and are disease-free. They must have good organ function, agree to contraception if applicable, and not be pregnant or breastfeeding. Excluded are those with other cancers in the last 3 years, certain heart conditions, severe infections or lactose intolerance.

Inclusion Criteria

My melanoma has a BRAF V600 mutation.

My melanoma was surgically removed with clear margins and is stage II.

My blood counts for neutrophils, platelets, and hemoglobin are within the required range.

Exclusion Criteria

I have or am at risk for blocked veins in my eye.

I have not had another cancer or a condition shortening my life to under 5 years in the last 3 years.

My cancer has spread to lymph nodes or other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive encorafenib and binimetinib or placebo for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Treatment Details

Interventions

• Binimetinib
• Encorafenib

Trial Overview The trial is testing whether taking Encorafenib and Binimetinib for one year after surgery can prevent melanoma from coming back better than just watching and waiting (surveillance). Participants will either receive the drugs or placebo versions without knowing which they're getting.

Participant Groups

Group I: Arm A Experimental Treatment 1 Intervention

Encorafenib and Binimetinib

Group II: Arm B Placebo Group 1 Intervention

Placebo to match Encorafenib Placebo to match Binimetinib

Who Is Running the Clinical Trial?

Pierre Fabre Medicament

Lead Sponsor

Trials

83

Recruited

90,400+

Marie-Andrée Gamache

Pierre Fabre Medicament

Chief Executive Officer

MBA from HEC Montréal

Dr. Núria Perez-Cullell

Pierre Fabre Medicament

Chief Medical Officer since 2022

PhD in Pharmacy from the University of Barcelona

European Organisation for Research and Treatment of Cancer - EORTC

Collaborator

Trials

417

Recruited

166,000+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Encorafenib and binimetinib, a combination of a BRAF inhibitor and a MEK inhibitor, received FDA approval in June 2018 for treating patients with unresectable or metastatic melanoma that has specific BRAF mutations (V600E or V600K).

The combination therapy is also being explored in ongoing phase III clinical trials for metastatic colorectal cancer, indicating its potential broader application beyond melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encorafenib and Binimetinib: First Global Approvals. Shirley, M.[2019]

The combination of encorafenib and binimetinib has shown a median overall survival of 33.6 months in patients with advanced BRAFV600 mutation-positive melanoma, outperforming other BRAF/MEK inhibitor combinations that achieved 22 months.

Encorafenib's unique pharmacokinetics allow for prolonged binding and greater BRAF inhibition, which may lead to improved efficacy and better tolerability, with fewer side effects like pyrexia and photosensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations. Trojaniello, C., Festino, L., Vanella, V., et al.[2019]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The combination of encorafenib and binimetinib for treating BRAF-mutant advanced melanoma shows similar efficacy to existing treatments like dabrafenib+trametinib and vemurafenib+cobimetinib, based on clinical trial results.

This new combination has a lower incidence of certain side effects, such as pyrexia and photosensitivity, which can significantly improve the quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term efficacy of encorafenib plus binimetinib combined treatment: case report.] Spagnolo, F.[2021]

In a phase II study involving 98 patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC), the combination of encorafenib and binimetinib achieved a confirmed objective response rate of 75% in treatment-naïve patients and 46% in previously treated patients, indicating significant efficacy.

The treatment was generally well-tolerated, with common side effects including nausea (50%) and diarrhea (43%), but it also led to dose reductions in 24% of patients and one serious adverse event of intracranial hemorrhage, highlighting the importance of monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. Riely, GJ., Smit, EF., Ahn, MJ., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma. Rose, AAN.[2019]

A 56-year-old woman experienced transient visual symptoms, including blurry vision and colored halos, after starting Encorafenib/Binimetinib for metastatic melanoma, indicating potential retinal side effects of the treatment.

Despite the initial symptoms being linked to subretinal fluid (SRF), the patient later experienced similar visual disturbances without any detectable SRF, suggesting that Binimetinib may cause intermittent visual symptoms even after fluid resolution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visual symptoms in a patient treated with MEK inhibitors. Tibaldi, T., Roccuzzo, G., Fazio, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

COLUMBUS 5-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Encorafenib and Binimetinib: First Global Approvals. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations. [2019]

4. England pubmed.ncbi.nlm.nih.gov

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. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

[Long-term efficacy of encorafenib plus binimetinib combined treatment: case report.] [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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]

8. Spain pubmed.ncbi.nlm.nih.gov

Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Visual symptoms in a patient treated with MEK inhibitors. [2022]