Encorafenib + Binimetinib for Melanoma

(COLUMBUS-AD Trial)

Not currently recruiting at 219 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of two drugs, encorafenib (Braftovi) and binimetinib (Mektovi), for treating melanoma with the BRAF V600E/K mutation. The researchers aim to determine if these drugs can better prevent cancer recurrence compared to simply monitoring the patient's condition. They seek participants who have had stage II melanoma surgically removed, tested positive for the BRAF mutation, and currently show no signs of the disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

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

Research shows that the combination of encorafenib and binimetinib is generally safe and well-tolerated. Studies have found that patients with BRAF V600E/K mutant melanoma experienced good safety results with these medications.

In earlier studies, patients taking this combination did not see significant cancer growth for several months. This suggests the treatment is effective and manageable in terms of side effects. The good safety profile indicates that severe side effects were uncommon, making this treatment a viable option for managing melanoma with the BRAF mutation.

Overall, while no treatment is without risks, available evidence suggests that encorafenib and binimetinib are safe for patients with this specific type of melanoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Researchers are excited about Encorafenib and Binimetinib for treating melanoma because these drugs specifically target the proteins in cancer cells that drive tumor growth. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, these treatments focus on inhibiting the BRAF and MEK pathways, which are often mutated in melanoma. This targeted approach can potentially lead to fewer side effects and more effective management of the disease. By blocking these pathways, Encorafenib and Binimetinib could offer a more precise treatment option, potentially improving outcomes for patients with melanoma.

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

Research has shown that using the drugs encorafenib and binimetinib together may help treat melanoma with certain BRAF mutations. In this trial, participants in Arm A will receive this combination. Earlier studies found that patients taking these drugs lived for about 36.8 months on average, compared to 19.3 months with other treatments. This suggests the combination could nearly double survival time for some patients. Additionally, about 69.4% of patients experienced tumor shrinkage or disappearance, indicating that this drug combo might effectively manage this type of melanoma. ^{1 4 6 7 8}

Who Is on the Research Team?

Alexander C.J. van AKKOOI, MD, PhD

Principal Investigator

European Organisation for Research and Treatment of Cancer - EORTC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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.

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. braftovi.pfizerpro.com braftovi.pfizerpro.com/mektovi-m/overall-survival

Overall survival (OS) Review overall survival (OS) data from the COLUMBUS trial with BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) and vemurafenib. See safety information.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924007299

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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40411977/

Results from the Dutch Melanoma Treatment Registry Encorafenib/binimetinib was the first-line treatment in 64 % of all patients, while 36 % had prior immunotherapy. Overall, the ORR was 69.4 %, ...

4. curemelanoma.org curemelanoma.org/patient-eng/melanoma-treatment/options/encorafenib-braftovi-binimetinib-mektovi

Encorafenib (Braftovi) + Binimetinib (Mektovi) In data presented at the American Society of Clinical Oncology (ASCO) conference in June, the combination demonstrated overall survival (OS) of 33.6 months and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12416198/

COLUMBUS part 1–7-year results for encorafenib and ... Seven-year melanoma-specific survival rates were 32% with enco/bini (encorafenib plus binimetinib), 20% with vemurafenib, and almost 34% with encorafenib ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9916040/

A Randomized, Open-Label, Phase III Trial of Encorafenib ... In conclusion, 35% of patients with unresectable or metastatic BRAF V600–mutant melanoma treated with encorafenib plus binimetinib in COLUMBUS were alive after ...

7. braftovi.com braftovi.com/m

BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) People taking BRAFTOVI + MEKTOVI lived without their cancer growing, spreading, or getting worse for a median of 14.9 months compared with a median of 7.3 ...

8. dailynews.ascopubs.org dailynews.ascopubs.org/do/encorafenib-binimetinib-displays-promising-safety-efficacy-signals-braf-v600e-k-mutated

Encorafenib + Binimetinib Displays Promising Safety ... “We've been able to show that treatment with encorafenib/binimetinib for BRAF-mutant stage IIB/IIC melanoma is safe and tolerable—and I think ...