Encorafenib + Binimetinib Access for Cancer

Recruiting at 50 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Pfizer

Must be taking: Encorafenib, Binimetinib

Disqualifiers: Not in prior study, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial continues the use of cancer medications encorafenib and binimetinib for patients who benefited from them in previous studies. The drugs work by blocking proteins that help cancer cells grow. Encorafenib and binimetinib were first approved for use in combination to treat metastatic melanoma with specific BRAF mutations.

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 data supports the effectiveness of the drug combination Encorafenib and Binimetinib for cancer treatment?

Research shows that the combination of Encorafenib and Binimetinib is effective in treating advanced melanoma with a specific gene mutation, improving survival rates and quality of life compared to other treatments. This combination is also being studied for its potential in treating other types of cancer. ^{1 2 3 4 5}

Is the combination of Encorafenib and Binimetinib safe for human use?

The combination of Encorafenib and Binimetinib has been shown to have an acceptable safety profile in patients with certain types of cancer, such as metastatic melanoma and non-small-cell lung cancer. Some side effects like fever and skin sensitivity are less common compared to other similar treatments, which can improve patients' quality of life. ^{1 4 5 6 7}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Binimetinib (Kinase Inhibitor)
• Encorafenib (Kinase Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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 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]

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 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]

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 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]

References

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

Encorafenib and Binimetinib: First Global Approvals. [2019]

2. 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]

3. 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]

4. United States 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. [2021]

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

The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma. [2019]