Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Stay on your current meds
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this study is to assess rate of disease relapse and hazard rate of disease relapse after neoadjuvant therapy based on the statuses of pathologic complete response or non-pathologic complete response, and postoperative adjuvant therapy.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot use certain prohibited medications, including some herbal supplements and foods, within one week before starting the study treatment. It's best to discuss your current medications with the trial team.
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. This combination also has fewer side effects like fever and skin sensitivity, making it a promising option for treatment.
12345Is 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.
16789How is the drug combination of Encorafenib and Binimetinib unique for treating melanoma?
The combination of Encorafenib and Binimetinib is unique because it offers improved overall survival and progression-free survival for patients with BRAF-mutant melanoma compared to other BRAF/MEK inhibitor combinations. It also has fewer side effects like fever and skin sensitivity, making it potentially more tolerable for patients.
12345Eligibility Criteria
Adults with melanoma that has a BRAFV600 mutation, either stage III or IV, can join this trial. They must have good blood counts and organ function, agree to use contraception, and not have had certain treatments or uncontrolled health issues recently. Those with specific drug allergies or who are pregnant cannot participate.Inclusion Criteria
I am a woman who can have children, tested negative for pregnancy, and agree to use effective birth control.
My melanoma has a BRAFV600 mutation and is either stage III or IV.
I agree to use effective birth control methods.
I am 18 years old or older.
I can take care of myself but might not be able to do heavy physical work.
My melanoma diagnosis was confirmed through tissue examination.
Exclusion Criteria
I am not taking any medication or supplements that are not allowed in the study.
I will not consume grapefruit, pomegranates, star fruits, Seville oranges or their juices while taking encorafenib/binimetinib.
I have HIV without effective treatment and my viral load is not undetectable.
My condition worsened while I was on BRAF/MEK inhibitor therapy.
I haven't had major surgery or radiotherapy in the last 2 weeks.
I had to stop taking encorafenib/binimetinib due to side effects.
I do not have serious heart issues like untreated heart failure or irregular heartbeats.
I do not have uncontrolled brain tumors or cancer in my brain's lining.
I have a history of blocked veins in my retina.
I have hepatitis C that is either untreated, not cured, or currently being treated.
Participant Groups
The study is testing the effectiveness of Encorafenib and Binimetinib pills before surgery (neoadjuvant therapy) in melanoma patients with a BRAF mutation. After surgery (adjuvant therapy), Nivolumab will be used depending on the initial response to treatment.
4Treatment groups
Experimental Treatment
Active Control
Group I: Nivolumab after Non-Pathologic Complete ResponseExperimental Treatment3 Interventions
Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will receive nivolumab for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.
Group II: Encorafenib and Binimetinib after Pathologic Complete ResponseExperimental Treatment2 Interventions
Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.
Group III: Encorafenib and Binimetinib after Non-Pathologic Complete ResponseExperimental Treatment2 Interventions
Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.
Group IV: SurveillanceActive Control2 Interventions
Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will receive adjuvant treatment for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.
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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who is running the clinical trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
PfizerIndustry Sponsor
References
Encorafenib and Binimetinib: First Global Approvals. [2019]Encorafenib (Braftovi™), a BRAF inhibitor, and binimetinib (Mektovi®), a MEK inhibitor, are two orally bioavailable drugs developed by Array BioPharma. In June 2018 they each received their first global approval, in the USA, for use in combination, for patients with unresectable or metastatic melanoma with a BRAFV600E or -V600K mutation as detected by an FDA-approved test. Registration applications for encorafenib and binimetinib for use in combination in the treatment of BRAF-mutation-positive advanced melanoma have also been submitted in the EU, Australia, Switzerland and Japan, with the EMA Committee for Medicinal Products for Human Use adopting a positive opinion in July 2018 towards granting the drugs marketing authorizations in the EU. Encorafenib plus binimetinib combination therapy is also in ongoing phase III clinical development in the treatment of metastatic colorectal cancer. This article summarizes the milestones in the development of encorafenib and binimetinib leading to these first approvals for the treatment of BRAFV600E or -V600K-mutation-positive unresectable or metastatic 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. [2019]Label="BACKGROUND">Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAFV600-mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival.
COLUMBUS 5-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF. [2023]Label="WHAT IS THIS SUMMARY ABOUT?" NlmCategory="UNASSIGNED">Here, we summarize the 5-year results from part 1 of the COLUMBUS clinical study, which looked at the combination treatment of encorafenib plus binimetinib in people with a specific type of skin cancer called melanoma. Encorafenib (BRAFTOVI®) and binimetinib (MEKTOVI®) are medicines used to treat a type of melanoma that has a change in the BRAF gene, called advanced or metastatic BRAF V600-mutant melanoma. Participants with advanced or metastatic BRAF V600-mutant melanoma took either encorafenib plus binimetinib together (COMBO group), compared with encorafenib alone (ENCO group) or vemurafenib (ZELBORAF®) alone (VEMU group).
Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations. [2019]Label="INTRODUCTION" NlmCategory="BACKGROUND">Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAFV600 mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge. Areas covered: Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/MEK inhibitor combinations. Expert opinion: While other BRAF/MEK inhibitor combinations have achieved a median overall survival (OS) of 22 months, patients with advanced BRAF mutation-positive melanoma treated with encorafenib plus binimetinib achieved a median OS of 33.6 months in the phase III COLUMBUS trial. PFS also appears to be improved with encorafenib plus binimetinib. This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of pyrexia and photosensitivity. Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.
[Long-term efficacy of encorafenib plus binimetinib combined treatment: case report.] [2021]Combination treatment with BRAF plus MEK inhibitors is a standard of care in patients with BRAF-mutant advanced melanoma. In addition to dabrafenib+trametinib and vemurafenib+cobimetinib, a new combination of BRAF and MEK inhibitors, encorafenib and binimetinib, was recently introduced into clinical practice. Encorafenib plus binimetinib achieved similar efficacy to that observed with previously available combinations, but incidence of some toxicities such as pyrexia and photosensitivity, which have a relevant impact on patients quality of life, is lower. In this article, the case of a patient who received encorafenib and binimetinib within the phase 3 trial COLUMBUS is presented and discussed, with a focus on the clinical management during the pandemic caused by SARS-CoV-2 virus.
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. [2023]Label="PURPOSE">The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAFV600E/K-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC).
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]In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment. Here, results on health-related quality of life (HRQoL) are presented.
Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma. [2019]BRAF is a constituent of the mitogen-activated protein kinase (MAPK) signaling pathway, which serves to activate downstream MEK, and is one of the most commonly mutated oncogenes in human tumors. Indeed, BRAF V600 mutations are present in approximately 40% of metastatic melanoma tumors. Encorafenib (LGX-818, Braftovi) and binimetinib (MEK-162, Mektovi) are small-molecule inhibitors of BRAF and MEK, respectively. BRAF and MEK inhibitors have been shown to improve overall and progression-free survival among patients with metastatic melanoma. Of these inhibitors, encorafenib and binimetinib are the newest combination, which received approval by the Food and Drug Administration (FDA) for the treatment of BRAF V600E/K-mutated melanoma in June 2018. This review will focus on the preclinical pharmacology, pharmacokinetics and clinical utility of encorafenib and binimetinib in BRAF V600-mutated melanoma.
Visual symptoms in a patient treated with MEK inhibitors. [2022]to report an uncommon presentation of Encorafenib-Binimetinib retinal side effects.