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A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma
Study Purpose
The purpose of this study is to learn about the effects of three study medicines (encorafenib, binimetinib, and pembrolizumab) given together for the treatment of melanoma that:
- - 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.
Recruitment Criteria
|
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
|
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 18 Years and Over |
| Gender | All |
Inclusion Criteria:
- - Male or female participants ≥ 18 years at the time of informed consent.
- - 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.
- - Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study (including, but not limited to, a participant who is rapidly progressing or has clinically significant tumor related symptoms, in the judgment of the investigator).
- - 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).
- - 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 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.
Trial Details
|
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT04657991 |
|
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
|
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Pfizer |
|
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Pfizer CT.gov Call Center |
| Principal Investigator Affiliation | Pfizer |
|
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
| Overall Status | Active, not recruiting |
| Countries | Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Mexico, New Zealand, Norway, Poland, Russia, Slovakia, South Africa, Spain, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States |
|
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Melanoma |
| Study Website: | View Trial Website |
This study will compare the efficacy, safety, and tolerability of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus placebo plus pembrolizumab (Control Arm) in participants with metastatic or unresectable locally advanced BRAF V600E/K mutation-positive melanoma. The study will have an open-label safety lead-in (SLI) phase to determine the safety recommend Phase 3 dose (RP3D) and pharmacokinetics (PK) of encorafenib and binimetinib plus pembrolizumab combination therapy prior to initiation of the randomized Phase 3 part of the study. Two dose levels of encorafenib in combination with binimetinib plus pembrolizumab will be explored in parallel. A minimum of 12 evaluable participants will be enrolled per dose level. During the double-blind randomized Phase 3 part of the study, approximately 216 eligible participants will be randomized in a 1:1 ratio to the Triplet Arm (at RP3D determined in the SLI) or Control Arm (approximately 108 participants per arm). Randomization will be stratified by prior systemic adjuvant therapy and stage of disease by AJCC (ED8).
Arms
Experimental: Triplet Arm
Encorafenib and Binimetinib in combination with Pembrolizumab
Active Comparator: Control Arm
Pembrolizumab
Interventions
Drug: - Encorafenib
Encorafenib
Drug: - Binimetinib
Binimetinib
Drug: - Pembrolizumab
Pembrolizumab
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
AdventHealth Orlando Infusion Center
Orlando 4167147, Florida 4155751, 32804
Status
Address
AdventHealth Orlando, Investigational Drug Services
Orlando 4167147, Florida 4155751, 32804
Status
Address
AdventHealth Orlando
Orlando 4167147, Florida 4155751, 32804
Status
Address
The University of Kansas Clinical Research Center
Fairway 4271358, Kansas 4273857, 66205
Status
Address
The University of Kansas Cancer Center - Overland Park
Overland Park 4276873, Kansas 4273857, 66210
Status
Address
The University of Kansas Cancer Center, Investigational Drug Services
Westwood 4281639, Kansas 4273857, 66205
Status
Address
The University of Kansas Cancer Center
Westwood 4281639, Kansas 4273857, 66205
Status
Address
Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926, 02114
Status
Address
Ophthalmic Consultants of Boston Inc (OCB)
Boston 4930956, Massachusetts 6254926, 02114
Status
Address
University of Cincinnati Medical Center
Cincinnati 4508722, Ohio 5165418, 45219
Status
Address
University of Cincinnati Medical Center
West Chester 4520522, Ohio 5165418, 45069
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Address
University of Tennessee Medical Center
Knoxville 4634946, Tennessee 4662168, 37920
Status
Address
Sarah Cannon Research Institute
Nashville 4644585, Tennessee 4662168, 37203
Status
Address
Tennessee Oncology, PLLC
Nashville 4644585, Tennessee 4662168, 37203
International Sites
Status
Address
Instituto Alexander Fleming
CABA, Buenos Aires 3435907, C1426ANZ
Status
Address
Clinica Viedma S. A
Viedma 3832899, Río Negro Province 3838830, 8500
Status
Address
Medizinische Universität Graz
Graz 2778067, , 8036
Status
Address
Cliniques universitaires Saint-Luc
Brussels 2800866, , 1200
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Address
Instituto de Oncologia do Paraná - IOP Matriz Mateus Leme
Curitiba 3464975, Paraná 3455077, 80520-174
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Address
Instituto de Oncologia do Paraná - IOP Oncoville
Curitiba 3464975, Paraná 3455077, 82305-100
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Address
Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
Rio de Janeiro 3451190, Rio de Janeiro 3451189, 20220-410
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Address
Hospital de Clínicas de Passo Fundo
Passo Fundo 3454857, Rio Grande do Sul 3451133, 99010-260
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Address
Hospital de Clinicas de Porto Alegre
Porto Alegre 3452925, Rio Grande do Sul 3451133, 90035-903
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Address
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos 3470451, São Paulo 3448433, 14784-400
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Address
Hospital Sírio-Libanês - Unidade Bela Vista
São Paulo 3448439, , 01308-050
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Address
Complex Oncology Center - Plovdiv EOOD
Plovdiv 728193, , 4004
Status
Address
Medical Center Nadezhda Clinical EOOD
Sofia 727011, , 1373
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Address
Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda EAD
Sofia 727011, , 1407
Status
Address
Umhato Ead
Sofia 727011, , 1756
Status
Address
CIUSSS du Saguenay-Lac-Saint-Jean
Chicoutimi 5921225, Quebec 6115047, G7H 5H6
Status
Address
Olomouc University Hospital
Olomouc 3069011, Olomoucký kraj 3339542, 779 00
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Address
Fakultni nemocnice Ostrava
Ostrava-Poruba, , 708 52
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Address
Fakultni nemocnice Bulovka
Praha 8-Liben, , 180 81
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Address
Tampereen yliopistollinen sairaala
Tampere 634963, Pirkanmaa 830704, 33520
Status
Address
Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
Helsinki 658225, , 00029
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Address
CHU d'Amiens - Hôpital Nord
Amiens 3037854, , 80054
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Address
CHU Grenoble Alpes
La Tronche 3006131, , 38700
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Address
Hôpital Lyon Sud
Pierre-Bénite 2987314, , 69310
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Address
CHU de Poitiers
Poitiers 2986495, , 86000
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Address
Universitaetsklinikum Tuebingen
Tübingen 2820860, Baden-Wurttemberg 2953481, 72076
Status
Address
Klinik und Poliklinik für Dermatologie und Allergologie
München 2867713, Bavaria 2951839, 80337
Status
Address
Universitätsklinikum Bonn
Bonn 2946447, North Rhine-Westphalia 2861876, 53127
Status
Address
Johannes Wesling Klinikum Minden
Minden 2871039, North Rhine-Westphalia 2861876, 32429
Status
Address
Universitätsmedizin Johannes Gutenberg Universität Mainz
Mainz 2874225, Rhineland-Palatinate 2847618, 55131
Status
Address
Universitaetsklinikum Carl Gustav Carus, Technischen Universitaet Dresden
Dresden 2935022, Saxony 2842566, 01307
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Address
Universitätsklinikum Leipzig
Leipzig 2879139, Saxony 2842566, 04103
Status
Address
Universitaetsklinikum Schleswig-Holstein Campus Kiel
Kiel 2891122, Schleswig-Holstein 2838632, 24105
Status
Address
Universitätsklinikum Schleswig-Holstein
Lübeck 2875601, Schleswig-Holstein 2838632, 23538
Status
Address
SRH Wald-Klinikum Gera
Gera 2921232, Thuringia 2822542, 07548
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Address
Charité Universitaetsmedizin Berlin - Campus Mitte
Berlin 2950159, , 10117
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Address
HELIOS Klinikum Erfurt
Erfurt 2929670, , 99089
Status
Address
Universitätsklinikum Essen (AöR)
Essen 2928810, , 45147
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Address
Universitaetsklinikum Halle - Universitaetsklinik und Poliklinik fuer Dermatologie und Venerologie
Halle 2911522, , 06120
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Address
Universitaetsklinikum Hamburg-Eppendorf
Hamburg 2911298, , 20246
Status
Address
Medizinische Hochschule Hannover
Hanover 2910831, , 30625
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Address
Universitätsklinikum Heidelberg
Heidelberg 2907911, , 69120
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Address
University Hospital Muenster
Münster 2867543, , 48149
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Address
Fachklinik Hornheide
Münster 2867543, , 48157
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Address
Klinikum Nürnberg Nord
Nuremberg 2861650, , 90419
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Address
Universitätsklinikum Regensburg
Regensburg 2849483, , 93053
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Address
General Hospital of Athens "Laiko"
Athens 264371, Attikí, 11527
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Address
Laiko Hospital
Athens 264371, Attikí, 11527
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Address
Pécsi Tudományegyetem Klinikai Központ
Pécs 3046526, Baranya 3055399, 7632
Status
Address
Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház
Szolnok 715126, Jász-Nagykun-Szolnok 719637, 5004
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Address
Semmelweis Egyetem
Budapest 3054643, , 1085
Status
Address
Orszagos Onkologiai Intezet
Budapest 3054643, , 1122
Status
Address
Debreceni Egyetem Klinikai Kozpont
Debrecen 721472, , 4032
Status
Address
Szent-Gyorgyi Albert Klinikai Kozpont
Szeged 715429, , 6720
Status
Address
Soroka University Medical Center
Beersheba 295530, , 8410101
Status
Address
Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem
Jerusalem 281184, , 9112001
Status
Address
Azienda Sanitaria Universitaria Friuli Centrale
Udine 3165072, Friuli Venezia Giulia 3176525, 33100
Status
Address
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan 6951411, MI, 20133
Status
Address
Istituto Dermopatico dell'Immacolata (IDI-IRCCS)
Roma 8957247, RM, 00167
Status
Address
A.O.U.S. Policlinico "Le Scotte"
Siena 3166548, SI, 53100
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Address
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
Candiolo 3180861, Torino, 10060
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Address
Istituto Tumori Giovanni Paolo II
Bari 3182351, , 70124
Status
Address
IRCCS Ospedale Policlinico San Martino
Genova 8969657, , 16132
Status
Address
Istituto Europeo di Oncologia IRCCS
Milan 6951411, , 20141
Status
Address
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
Napoli 9031661, , 80131
Status
Address
Istituto Oncologico Veneto IOV - IRCCS
Padua 3171728, , 35128
Status
Address
AO di Perugia - Ospedale S. Maria della Misericordia, S.C Oncologia Medica
Perugia 3171180, , 06132
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Address
Istituto Nazionale Tumori Regina Elena
Roma 8957247, , 00144
Status
Address
Preparaciones Oncológicas S.C.
León 3998655, Guanajuato 4005267, 37178
Status
Address
ONCARE Viaducto Nápoles
Benito Juárez 6957079, Mexico City 3527646, 03810
Status
Address
I Can Oncology Center S.A. de C.V.
Monterrey 3995465, Nuevo León 3522542, 64710
Status
Address
BRCR Global Mexico - CDMX
Mexico City 3530597, , 01120
Status
Address
El Cielo Medical Center RSB, S.C
Puebla City 3521081, , 72160
Status
Address
Palmerston North Hospital
Palmerston North 2185018, Manawatu, 4414
Status
Address
Oslo universitetssykehus, Radiumhospitalet
Oslo 3143244, , 0379
Status
Address
Jagiellońskie Centrum Innowacji Sp. z o .o.
Krakow 3094802, , 30-348
Status
Address
Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
Poznan 3088171, , 60-780
Status
Address
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw 756135, , 02-781
Status
Address
Private Medical Institution "Euromedservice"
Pushkin 504003, Sankt-Peterburg 536203, 196603
Status
Address
Ars Medika Center, LLC
Kaliningrad 554234, ,
Status
Address
BIH of Omsk Region "Clinical Oncological Dispensary"
Omsk 1496153, , 644046
Status
Address
Eurocityclinic LLC
Saint Petersburg 498817, , 197022
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Address
Onkologicky ustav sv. Alzbety, s.r.o.
Bratislava 3060972, , 812 50
Status
Address
Narodny onkologicky ustav
Bratislava 3060972, , 833 10
Status
Address
Vychodoslovensky onkologicky ustav, a.s.
Košice 724443, , 04191
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Address
Nemocnica na okraji mesta, n.o.
Partizánske 3058268, , 95801
Status
Address
POKO Poprad, s.r.o.
Poprad 723846, , 058 01
Status
Address
WCR Office
Johannesburg 993800, Gauteng 1085594, 2193
Status
Address
Wits Clinical Research
Johannesburg 993800, Gauteng 1085594, 2193
Status
Address
Sandton Oncology Medical Group (Pty) Ltd
Johannesburg 993800, Gauteng 1085594, 2196
Status
Address
Drs Alberts, Bouwer and Jordaan Inc.
Pretoria 964137, Gauteng 1085594, 0081
Status
Address
ICO-Badalona Hospital Germans Trias i Pujol
Badalona 3129028, Barcelona, 08916
Status
Address
Hospital Universitario Marqués de Valdecilla
Santander 3109718, Cantabria 3336898, 39008
Status
Address
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda 3117667, Madrid 3117732, 28222
Status
Address
Hospital Clinico Universitario Virgen de la Arrixaca
El Palmar 2518294, Murcia 2513413, 30120
Status
Address
CHUAC-Hospital Teresa Herrera
A Coruña 3119841, , 15006
Status
Address
Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
Barcelona 3128760, , 08035
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Address
Hospital Clinic Barcelona
Barcelona 3128760, , 08036
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Address
Hospital de la Santa Creu i Sant Pau
Barcelona 3128760, , 08041
Status
Address
Hospital Universitario Reina Sofía
Córdoba 2519240, , 14004
Status
Address
Complejo Hospitalario de Jaen
Jaén 2516395, , 23007
Status
Address
Hospital Universitario Arnau de Vilanova
Lleida 3118514, , 25198
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Address
Hospital Universitario Ramón y Cajal
Madrid 3117735, , 28034
Status
Address
Hospital Regional Universitario de Malaga - Hospital Civil
Málaga 2514256, , 29011
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Address
Hospital Universitario Virgen Macarena
Seville 2510911, , 41009
Status
Address
Hospital Universitario Virgen del Rocio
Seville 2510911, , 41013
Status
Address
Fundacion Instituto Valenciano de Oncologia
Valencia 2509954, , 46009
Status
Address
Hospital Universitario Miguel Servet
Zaragoza 3104324, , 50009
Status
Address
UniversitätsSpital Zürich
Zürich Flughafen, , 8058
Status
Address
Istanbul University Cerrahpasa Medical Faculty Hospital
Istanbul 745044, İ̇stanbul, 34098
Status
Address
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul 745044, İ̇stanbul, 34722
Status
Address
Memorial Ankara Hastanesi
Ankara 323786, , 06520
Status
Address
CNI KRC "Regional Cardiology Centre"
Kharkiv 706483, , 61166
Status
Address
National Cancer Institute
Kyiv 703448, , 03022
Status
Address
Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Oncological Regional Therapeutical
Lviv 702550, , 79031
Status
Address
Derzhavna ustanova Instytut zahalnoi ta nevidkladnoi khirurhii im.V.T.Zaitseva Natsionalnoi akademii
M. Kharkiv, , 61103
Status
Address
St. Bartholomew's Hospital, Barts Health NHS Trust
London 2643743, , EC1A 7BE
Status
Address
The South West Wales Cancer Institute, Swansea Bay University Health Board
Swansea 2636432, , SA2 8QA
