A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma
NCT ID: NCT04657991
Last Updated: 2025-08-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
257 participants
INTERVENTIONAL
2021-01-15
2026-03-23
Brief Summary
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* is advanced or metastatic (spread to other parts of the body);
* has a certain type of abnormal gene called "BRAF"; and
* has not received prior treatment.
All participants in this study will receive pembrolizumab at the study clinic once every 3 weeks as an intravenous (IV) infusion (given directly into a vein). In addition, half of the participants will take encorafenib and binimetinib orally (by mouth) at home every day.
Participants may receive pembrolizumab for up to two years. Those participants taking encorafenib and binimetinib can continue until their melanoma is no longer responding. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Triplet Arm
Encorafenib and Binimetinib in combination with Pembrolizumab
Encorafenib
Encorafenib
Binimetinib
Binimetinib
Pembrolizumab
Pembrolizumab
Control Arm
Pembrolizumab
Pembrolizumab
Pembrolizumab
Interventions
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Encorafenib
Encorafenib
Binimetinib
Binimetinib
Pembrolizumab
Pembrolizumab
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
* Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
* Presence of at least 1 measurable lesion as detected by radiological and/or photographic methods according to RECIST v1.1.
* ECOG performance status 0 or 1.
* Documented evidence of a BRAF V600E or V600K mutation in melanoma tumor tissue as previously determined by either PCR or NGS-based local laboratory assay (eg, US FDA-approved test, CE-marked \[European conformity\] in vitro diagnostic in EU countries, or equivalent), obtained during the course of normal clinical care, in a CLIA- or similarly certified laboratory.
* Submission of adequate tumor tissue (archival or newly obtained; block or slides to the sponsor central laboratory(ies) during the screening period and prior to enrollment (SLI)/randomization (Phase 3).
* Have not received prior first-line systemic therapy for metastatic or unresectable locally advanced melanoma.
* Adequate bone marrow function, hepatic and renal function.
* Capable of giving signed informed consent.
Exclusion Criteria
* Mucosal or ocular melanoma.
* Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
* Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
* Unable to swallow, retain, and absorb oral medications.
* Impairment of GI function or disease which may significantly alter the absorption of oral study intervention (eg, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, including malabsorption syndrome secondary to prior GI surgery).
* Clinically significant cardiovascular diseases,
* History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to enrollment (SLI)/randomization (Phase 3). Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (ie, massive or sub-massive) deep vein thrombosis or pulmonary emboli.
* History or current evidence of RVO or current risk factors for RVO (eg, uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
* Concurrent neuromuscular disorder that is associated with the potential of elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
* Current noninfectious pneumonitis or history of noninfectious pneumonitis requiring steroids, or history of radiation pnuemonitis
* Evidence of HBV or HCV infection.
* Known history of a positive test for HIV or known AIDS.
* Any active infection requiring systemic therapeutic treatment within 2 weeks prior to enrollment (SLI)/ randomization (Phase 3).
* Participants with prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
* Concurrent or previous other malignancy within 2 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen's disease and Gleason ≤ 6 prostate cancer. Participants with a history of other curatively treated cancers must be reviewed with the sponsor or designee prior to entering the study.
* Participants who previously received and subsequently discontinued encorafenib and/or binimetinib and/or anti-PD-1/-L1 due to severe toxicity.
* For participants in the SLI only: Current use or anticipated need for food or drugs that are known moderate or strong CYP3A4 inhibitors during screening and through the DLT-evaluation period
* Participant has not recovered to Grade ≤ 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before enrollment (SLI)/ randomization (Phase 3).
* Receipt of protocol defined medications or treatments outside of required intervals before enrollment (SLI)/randomization (Phase 3):
* Previous administration with an investigational drug ≤ 6 months prior to enrollment (SLI)/randomization (Phase 3).
* Known sensitivity or contraindication to any component of study intervention (encorafenib, binimetinib and pembrolizumab), or their excipients.
* Pregnant, confirmed by a positive β-hCG laboratory test result, or is breastfeeding (lactating).
* Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
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AdventHealth Orlando Infusion Center
Orlando, Florida, United States
AdventHealth Orlando, Investigational Drug Services
Orlando, Florida, United States
AdventHealth Orlando
Orlando, Florida, United States
The University of Kansas Clinical Research Center
Fairway, Kansas, United States
The University of Kansas Cancer Center - Overland Park
Overland Park, Kansas, United States
The University of Kansas Cancer Center, Investigational Drug Services
Westwood, Kansas, United States
The University of Kansas Cancer Center
Westwood, Kansas, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Ophthalmic Consultants of Boston Inc (OCB)
Boston, Massachusetts, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
University of Cincinnati Medical Center
West Chester, Ohio, United States
University of Tennessee Medical Center
Knoxville, Tennessee, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, United States
Instituto Alexander Fleming
CABA, Buenos Aires, Argentina
Clinica Viedma S. A
Viedma, Río Negro Province, Argentina
Medizinische Universität Graz
Graz, , Austria
Cliniques universitaires Saint-Luc
Brussels, , Belgium
Instituto de Oncologia do Paraná - IOP Matriz Mateus Leme
Curitiba, Paraná, Brazil
Instituto de Oncologia do Paraná - IOP Oncoville
Curitiba, Paraná, Brazil
Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
Rio de Janeiro, Rio de Janeiro, Brazil
Hospital de Clínicas de Passo Fundo
Passo Fundo, Rio Grande do Sul, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos, São Paulo, Brazil
Hospital Sírio-Libanês - Unidade Bela Vista
São Paulo, , Brazil
Complex Oncology Center - Plovdiv EOOD
Plovdiv, , Bulgaria
Medical Center Nadezhda Clinical EOOD
Sofia, , Bulgaria
Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda EAD
Sofia, , Bulgaria
Umhato Ead
Sofia, , Bulgaria
CIUSSS du Saguenay-Lac-Saint-Jean
Chicoutimi, Quebec, Canada
Olomouc University Hospital
Olomouc, Olomoucký kraj, Czechia
Fakultni nemocnice Ostrava
Ostrava-Poruba, , Czechia
Fakultni nemocnice Bulovka
Praha 8-Liben, , Czechia
Tampereen yliopistollinen sairaala
Tampere, Pirkanmaa, Finland
Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
Helsinki, , Finland
CHU d'Amiens - Hôpital Nord
Amiens, , France
CHU Grenoble Alpes
La Tronche, , France
Hôpital Lyon Sud
Pierre-Bénite, , France
CHU de Poitiers
Poitiers, , France
Universitaetsklinikum Tuebingen
Tübingen, Baden-Wurttemberg, Germany
Klinik und Poliklinik für Dermatologie und Allergologie
München, Bavaria, Germany
Universitätsklinikum Bonn
Bonn, North Rhine-Westphalia, Germany
Johannes Wesling Klinikum Minden
Minden, North Rhine-Westphalia, Germany
Universitätsmedizin Johannes Gutenberg Universität Mainz
Mainz, Rhineland-Palatinate, Germany
Universitaetsklinikum Carl Gustav Carus, Technischen Universitaet Dresden
Dresden, Saxony, Germany
Universitätsklinikum Leipzig
Leipzig, Saxony, Germany
Universitaetsklinikum Schleswig-Holstein Campus Kiel
Kiel, Schleswig-Holstein, Germany
Universitätsklinikum Schleswig-Holstein
Lübeck, Schleswig-Holstein, Germany
SRH Wald-Klinikum Gera
Gera, Thuringia, Germany
Charité Universitaetsmedizin Berlin - Campus Mitte
Berlin, , Germany
HELIOS Klinikum Erfurt
Erfurt, , Germany
Universitätsklinikum Essen (AöR)
Essen, , Germany
Universitaetsklinikum Halle - Universitaetsklinik und Poliklinik fuer Dermatologie und Venerologie
Halle, , Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, , Germany
Medizinische Hochschule Hannover
Hanover, , Germany
Universitätsklinikum Heidelberg
Heidelberg, , Germany
University Hospital Muenster
Münster, , Germany
Fachklinik Hornheide
Münster, , Germany
Klinikum Nürnberg Nord
Nuremberg, , Germany
Universitätsklinikum Regensburg
Regensburg, , Germany
General Hospital of Athens "Laiko"
Athens, Attikí, Greece
Laiko Hospital
Athens, Attikí, Greece
Pécsi Tudományegyetem Klinikai Központ
Pécs, Baranya, Hungary
Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház
Szolnok, Jász-Nagykun-Szolnok, Hungary
Semmelweis Egyetem
Budapest, , Hungary
Orszagos Onkologiai Intezet
Budapest, , Hungary
Debreceni Egyetem Klinikai Kozpont
Debrecen, , Hungary
Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, , Hungary
Soroka University Medical Center
Beersheba, , Israel
Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem
Jerusalem, , Israel
Azienda Sanitaria Universitaria Friuli Centrale
Udine, Friuli Venezia Giulia, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, MI, Italy
Istituto Dermopatico dell'Immacolata (IDI-IRCCS)
Roma, RM, Italy
A.O.U.S. Policlinico "Le Scotte"
Siena, SI, Italy
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
Candiolo, Torino, Italy
Istituto Tumori Giovanni Paolo II
Bari, , Italy
IRCCS Ospedale Policlinico San Martino
Genova, , Italy
Istituto Europeo di Oncologia IRCCS
Milan, , Italy
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
Napoli, , Italy
Istituto Oncologico Veneto IOV - IRCCS
Padua, , Italy
AO di Perugia - Ospedale S. Maria della Misericordia, S.C Oncologia Medica
Perugia, , Italy
Istituto Nazionale Tumori Regina Elena
Roma, , Italy
Preparaciones Oncológicas S.C.
León, Guanajuato, Mexico
ONCARE Viaducto Nápoles
Benito Juárez, Mexico City, Mexico
I Can Oncology Center S.A. de C.V.
Monterrey, Nuevo León, Mexico
BRCR Global Mexico - CDMX
Mexico City, , Mexico
El Cielo Medical Center RSB, S.C
Puebla City, , Mexico
Palmerston North Hospital
Palmerston North, Manawatu, New Zealand
Oslo universitetssykehus, Radiumhospitalet
Oslo, , Norway
Jagiellońskie Centrum Innowacji Sp. z o .o.
Krakow, , Poland
Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
Poznan, , Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, , Poland
Private Medical Institution "Euromedservice"
Pushkin, Sankt-Peterburg, Russia
Ars Medika Center, LLC
Kaliningrad, , Russia
BIH of Omsk Region "Clinical Oncological Dispensary"
Omsk, , Russia
Eurocityclinic LLC
Saint Petersburg, , Russia
Onkologicky ustav sv. Alzbety, s.r.o.
Bratislava, , Slovakia
Narodny onkologicky ustav
Bratislava, , Slovakia
Vychodoslovensky onkologicky ustav, a.s.
Košice, , Slovakia
Nemocnica na okraji mesta, n.o.
Partizánske, , Slovakia
POKO Poprad, s.r.o.
Poprad, , Slovakia
WCR Office
Johannesburg, Gauteng, South Africa
Wits Clinical Research
Johannesburg, Gauteng, South Africa
Sandton Oncology Medical Group (Pty) Ltd
Johannesburg, Gauteng, South Africa
Drs Alberts, Bouwer and Jordaan Inc.
Pretoria, Gauteng, South Africa
ICO-Badalona Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
El Palmar, Murcia, Spain
CHUAC-Hospital Teresa Herrera
A Coruña, , Spain
Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
Barcelona, , Spain
Hospital Clinic Barcelona
Barcelona, , Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, , Spain
Hospital Universitario Reina Sofía
Córdoba, , Spain
Complejo Hospitalario de Jaen
Jaén, , Spain
Hospital Universitario Arnau de Vilanova
Lleida, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Hospital Regional Universitario de Malaga - Hospital Civil
Málaga, , Spain
Hospital Universitario Virgen Macarena
Seville, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Fundacion Instituto Valenciano de Oncologia
Valencia, , Spain
Hospital Universitario Miguel Servet
Zaragoza, , Spain
UniversitätsSpital Zürich
Zürich Flughafen, , Switzerland
Istanbul University Cerrahpasa Medical Faculty Hospital
Istanbul, İ̇stanbul, Turkey (Türkiye)
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul, İ̇stanbul, Turkey (Türkiye)
Memorial Ankara Hastanesi
Ankara, , Turkey (Türkiye)
CNI KRC "Regional Cardiology Centre"
Kharkiv, , Ukraine
National Cancer Institute
Kyiv, , Ukraine
Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Oncological Regional Therapeutical
Lviv, , Ukraine
Derzhavna ustanova Instytut zahalnoi ta nevidkladnoi khirurhii im.V.T.Zaitseva Natsionalnoi akademii
M. Kharkiv, , Ukraine
St. Bartholomew's Hospital, Barts Health NHS Trust
London, , United Kingdom
The South West Wales Cancer Institute, Swansea Bay University Health Board
Swansea, , United Kingdom
Countries
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References
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Schadendorf D, Dummer R, Robert C, Ribas A, Sullivan RJ, Panella T, McKean M, Santos ES, Brill K, Polli A, Pietro AD, Ascierto PA. STARBOARD: encorafenib + binimetinib + pembrolizumab for first-line metastatic/unresectable BRAF V600-mutant melanoma. Future Oncol. 2022 Jun;18(17):2041-2051. doi: 10.2217/fon-2021-1486. Epub 2022 Mar 11.
Zimmer L, Livingstone E, Krackhardt A, Schultz ES, Goppner D, Assaf C, Trebing D, Stelter K, Windemuth-Kieselbach C, Ugurel S, Schadendorf D. Encorafenib, binimetinib plus pembrolizumab triplet therapy in patients with advanced BRAFV600 mutant melanoma: safety and tolerability results from the phase I IMMU-TARGET trial. Eur J Cancer. 2021 Nov;158:72-84. doi: 10.1016/j.ejca.2021.09.011. Epub 2021 Oct 13.
Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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KEYNOTE-B80
Identifier Type: OTHER
Identifier Source: secondary_id
2024-512038-13-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
STARBOARD
Identifier Type: OTHER
Identifier Source: secondary_id
C4221016
Identifier Type: -
Identifier Source: org_study_id
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