Encorafenib + Binimetinib Access for Cancer

Recruiting at 75 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Pfizer

Must be taking: Encorafenib, Binimetinib

Disqualifiers: Not in prior study, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on providing continued access to the treatments encorafenib (Braftovi) and binimetinib (Mektovi) for cancer patients who have benefited from these medications in previous studies. The main goal is to ensure that those still experiencing positive effects can continue receiving the treatment while monitoring safety. Participants may receive a combination of encorafenib and binimetinib, just binimetinib, or encorafenib alone, based on their earlier treatment. Patients who participated in a previous trial with these drugs and continue to find them helpful might be suitable for this study. As a Phase 4 trial, this study involves treatments already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It seems focused on continuing the study medicines from previous trials.

What is the safety track record for these treatments?

A previous study found that people taking the combination of encorafenib and binimetinib experienced some serious side effects, including nausea, diarrhea, tiredness, and vomiting, with nausea affecting about 52% of patients. Serious side effects occurred in 38% of patients, and fatal reactions happened in 2% of cases.

For those using binimetinib alone, the safety profile was similar, with nausea and tiredness as the most common issues.

When combined with cetuximab, the side effects of encorafenib and binimetinib were generally similar to those known for each drug alone.

The combination of encorafenib, binimetinib, and ribociclib also showed similar safety results. Some patients reported serious side effects, but no new unexpected side effects emerged.

Overall, these treatments have been studied extensively, providing a good understanding of potential side effects. However, each person may react differently. Regular check-ups and reporting any issues to a doctor are important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Encorafenib and Binimetinib because, unlike traditional treatments for cancer that often target a single mutation or pathway, this combination targets multiple pathways involved in tumor growth. Encorafenib is a BRAF inhibitor, which specifically targets and inhibits the activity of the BRAF protein, a key player in cell growth and division in certain cancers. Binimetinib, on the other hand, is a MEK inhibitor, which blocks the MEK enzymes in the same pathway, potentially enhancing the effectiveness of the treatment by attacking the cancer from multiple angles. This dual approach has the potential to be more effective than standard therapies, which typically focus on one target at a time. The inclusion of additional combinations like Cetuximab or Ribociclib further diversifies the treatment strategy, aiming to improve outcomes by addressing different cancer pathways simultaneously.

What is the effectiveness track record for encorafenib and binimetinib in cancer treatment?

Research shows that using the drugs encorafenib and binimetinib together can significantly help treat certain cancers. In this trial, participants may receive this combination, which studies have found effective, with patients having specific BRAF mutations living for an average of 47.6 months without previous treatment. This drug combination works better than using each drug alone and usually has fewer serious side effects.

Additionally, some participants in this trial may receive a combination of encorafenib, binimetinib, and cetuximab, which has shown significant improvement in survival and response rates for patients with certain mutations. Another treatment arm in this trial includes encorafenib, binimetinib, and ribociclib, which has shown positive results in advanced cancer cases. Overall, these treatments have proven effective in clinical settings. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

The FLOTILLA study is for people with solid tumors who have previously benefited from encorafenib and/or binimetinib in earlier trials. They must be seeing ongoing benefits without severe side effects, as judged by their doctor, and agree to follow specific reproductive guidelines.

Inclusion Criteria

Participants must agree to follow the reproductive criteria as outlined in the applicable Encorafenib/Binimetinib Continuation Sub-Study Protocol

I am benefiting from an encorafenib/binimetinib study without severe side effects.

Exclusion Criteria

Any medical reason that, in the opinion of the investigator or sponsor, precludes the participant from inclusion in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive encorafenib and/or binimetinib at the same dose and frequency as in their prior study

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• Encorafenib

Trial Overview This trial provides continued access to encorafenib and binimetinib, alone or combined with ribociclib or cetuximab, for those previously treated with these drugs. The aim is safety monitoring while allowing participants to keep taking the same doses for up to five years.

How Is the Trial Designed?

Group I: Treatment of Encorafenib & Binimetinib & Ribociclib Experimental Treatment 1 Intervention

For those participants receiving treatment of encorafenib \& binimetinib \& ribociclib in parent studies

Group II: Treatment of Encorafenib & Binimetinib & Cetuximab Experimental Treatment 1 Intervention

For those participants receiving treatment of encorafenib \& binimetinib \& cetuximab in parent studies

Group III: Encorafenib only Treatment Experimental Treatment 1 Intervention

For those participants receiving encorafenib only treatment in parent studies

Group IV: Encorafenib & Binimetinib Treatment Experimental Treatment 1 Intervention

For those participants receiving encorafenib \& binimetinib treatment in parent studies.

Group V: Binimetinib only treatment Experimental Treatment 1 Intervention

For those participants receiving binimetinib treatment in parent studies

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

Approved in United States as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in European Union as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

The combination of encorafenib and binimetinib was found to be safe and showed promising activity in patients with BRAF V600E-mutant solid tumors, with a recommended phase 2 dose established for further studies.

In phase II, the treatment resulted in confirmed responses in 67% of BRAFi-naïve melanoma patients, indicating significant efficacy, while the most common serious side effect was increased alanine aminotransferase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Sullivan, RJ., Weber, J., Patel, S., et al.[2021]

In a study of melanoma patients treated with encorafenib and binimetinib, the most common skin-related side effects were palmoplantar hyperkeratosis (54%) and palmoplantar erythrodysesthesia (58%) when using encorafenib alone.

Encouragingly, the combination therapy of encorafenib and binimetinib was found to be well tolerated, with fewer cutaneous adverse events compared to established BRAF inhibitors, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma. Graf, NP., Koelblinger, P., Galliker, N., et al.[2019]

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 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 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, 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]

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. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-braftovir-mektovir-shows-sustained-long-term

Pfizer's BRAFTOVI® + MEKTOVI® Shows Sustained Long- ... BRAFTOVI + MEKTOVI continued to show a substantial median overall survival benefit of 47.6 months in treatment-naïve patients with BRAF ...

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

Overall survival (OS) In the COLUMBUS trial, cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 2.6% and basal cell carcinoma occurred in 1.6% of ...

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11213720/

A Practical Review of Encorafenib and Binimetinib Therapy ... While the incidence of cutaneous squamous cell carcinoma (SCC) was 12% with dabrafenib monotherapy in a previous trial, SCC was reported in 4% ...

5. braftovimektovi-melanoma.com braftovimektovi-melanoma.com/efficacy

efficacy Almost 1 in 4 patients remained progression free at 5 years with BRAFTOVI + MEKTOVI (23%)3. In the initial analysis (cut-off date May 2016), ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/210498s011lbl.pdf

MEKTOVI® (binimetinib) tablets, for oral use The data described in WARNINGS AND PRECAUTIONS reflect exposure of 192 patients with. BRAF V600 mutation-positive unresectable or metastatic melanoma to MEKTOVI ...

7. braftovi.pfizerpro.com braftovi.pfizerpro.com/mektovi-m/adverse-reactions

Adverse Reactions Use of BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) is associated with the following WARNINGS and PRECAUTIONS: New Primary Malignancies, Tumor Promotion ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/mektovi-epar-product-information_en.pdf

Mektovi, INN-binimetinib - European Medicines Agency The efficacy and safety of binimetinib in combination with encorafenib have been established only in patients with melanoma tumours expressing BRAF V600E ...

9. va.gov va.gov/formularyadvisor/DOC_PDF/MON_Binimetinib_MEKTOVI_Jun_2022.pdf

Binimetinib (MEKTOVI) National Drug Monograph Jun 2022 Dabrafenib + trametinib has the longest follow-up data for survival (5 years vs 4 years) shown in 3 clinical trials plus FDA indications in non-small cell lung ...

10. braftovi.pfizerpro.com braftovi.pfizerpro.com/mektovi-n/adverse-reactions

Adverse Reactions Select safety profile from the PHAROS trial · Serious ARs occurred in 38% of patients who received BRAFTOVI + MEKTOVI. · Fatal ARs occurred in 2% of patients who ...