A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma

April 12, 2024 updated by: Pfizer

A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS PLACEBO PLUS PEMBROLIZUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE METASTATIC OR UNRESECTABLE LOCALLY ADVANCED MELANOMA

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.

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

187

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
    • Buenos Aires
      • Caba, Buenos Aires, Argentina, C1426ANZ
        • Instituto Alexander Fleming
    • RÍO Negro
      • Viedma, RÍO Negro, Argentina, 8500
        • Clinica Viedma S. A
    • Santa FE
      • Rosario, Santa FE, Argentina, S2000KZE
        • Instituto De Oncologia De Rosario
  • Austria
      • Graz, Austria, 8036
        • Medizinische Universität Graz
    • Niederösterreich
      • St. Pölten, Niederösterreich, Austria, 3100
        • Universitätsklinikum St. Pölten
    • Oberösterreich
      • Linz, Oberösterreich, Austria, 4020
        • Ordensklinikum Linz GmbH Elisabethinen
    • Wien
      • Vienna, Wien, Austria, 1090
        • Medizinische Universitat Wien
  • Belgium
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
      • Haine Saint Paul, Belgium, 7100
        • Centre Hospitalier de Jolimont
      • Sint-Niklaas, Belgium, 9100
        • Vitaz
    • Bruxelles-capitale, Région DE
      • Brussels, Bruxelles-capitale, Région DE, Belgium, 1090
        • UZ Brussel
    • Oost-vlaanderen
      • Gent, Oost-vlaanderen, Belgium, 9000
        • UZ Gent
    • West-vlaanderen
      • Brugge, West-vlaanderen, Belgium, 8000
        • AZ Sint-Jan Brugge-Oostende AV
  • Brazil
      • São Paulo, Brazil, 01308-050
        • Hospital Sírio-Libanês - Unidade Bela Vista
    • Paraná
      • Curitiba, Paraná, Brazil, 80520-174
        • Instituto de Oncologia do Paraná - IOP Matriz Mateus Leme
      • Curitiba, Paraná, Brazil, 82305-100
        • Instituto de Oncologia do Paraná - IOP Oncoville
    • RIO Grande DO SUL
      • Porto Alegre, RIO Grande DO SUL, Brazil, 90035-903
        • Hospital de Clinicas de Porto Alegre
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20220-410
        • Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
    • RS
      • Passo Fundo, RS, Brazil, 99010-260
        • Hospital de Clínicas de Passo Fundo
    • SÃO Paulo
      • Barretos, SÃO Paulo, Brazil, 14784-400
        • Fundacao Pio XII - Hospital de Cancer de Barretos
  • Bulgaria
      • Plovdiv, Bulgaria, 4004
        • Complex Oncology Center - Plovdiv EOOD
      • Ruse, Bulgaria, 7002
        • Complex Oncology Center-Ruse EOOD
      • Sofia, Bulgaria, 1407
        • Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda EAD
      • Sofia, Bulgaria, 1373
        • Medical Center Nadezhda Clinical EOOD
      • Sofia, Bulgaria, 1756
        • Umhato Ead
  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston Health Sciences Centre-Kingston General Hospital Site
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 5H6
        • CIUSSS du Saguenay-Lac-Saint-Jean
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Centre - Glen Site
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N4H4
        • Saskatoon Cancer Center
  • Czechia
      • Brno, Czechia, 656 53
        • Masarykuv onkologicky ustav
      • Hradec Kralove, Czechia, 500 05
        • Fakultni nemocnice Hradec Kralove
      • Ostrava-Poruba, Czechia, 708 52
        • Fakultni nemocnice Ostrava
      • Praha 2, Czechia, 128 08
        • Vseobecna Fakultní Nemocnice
      • Praha 8-Liben, Czechia, 180 81
        • Fakultni nemocnice Bulovka
    • Olomoucký KRAJ
      • Olomouc, Olomoucký KRAJ, Czechia, 779 00
        • Fakultní nemocnice Olomouc
      • Olomouc, Olomoucký KRAJ, Czechia, 779 00
        • Olomouc University Hospital
  • Finland
      • Helsinki, Finland, 00029
        • Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
    • Pirkanmaa
      • Tampere, Pirkanmaa, Finland, 33520
        • Tampereen yliopistollinen Sairaala
  • France
      • Amiens, France, 80054
        • CHU d'Amiens - Hôpital Nord
      • Angers, France, 49000
        • CHU d'Angers
      • Bordeaux, France, 33075
        • Hopital Saint André
      • Boulogne-Billancourt, France, 92100
        • Hopital Ambroise Pare
      • Boulogne-Billancourt, France, 92104
        • Hopital Ambroise Pare
      • Dijon Cedex, France, 21079
        • CHU de Dijon Bourgogne
      • La Tronche, France, 38700
        • CHU Grenoble Alpes
      • Le Mans, France, 72037
        • CHG Le Mans
      • Lille, France, 59037
        • CHU de Lille - Hôpital Claude Huriez Service
      • Marseille, France, 13385
        • Hopital de la Timone
      • Pierre-Bénite, France, 69310
        • Hopital Lyon Sud
      • Poitiers, France, 86000
        • CHU De Poitiers
      • Rouen, France, 76031
        • Hôpital Charles Nicolle - CHU de Rouen
      • Saint-Etienne Cedex 2, France, 42055
        • CHU de Saint-Etienne - Hôpital Nord
      • Villejuif, France, 94800
        • Gustave Roussy
    • Cedex 9
      • Le Mans, Cedex 9, France, 72037
        • CHG Le Mans
    • Haute-normandie
      • Rouen, Haute-normandie, France, 76031
        • CHU Charles Nicolle
    • Nord
      • Lille, Nord, France, 59037
        • CHU de Lille - Hôpital Claude Huriez Service
  • Germany
      • Berlin, Germany, 12351
        • Vivantes Klinikum Neukölln
      • Berlin, Germany, 10117
        • Charité Universitaetsmedizin Berlin - Campus Mitte
      • Erfurt, Germany, 99089
        • Helios Klinikum Erfurt
      • Essen, Germany, 45147
        • Universitätsklinikum Essen (AöR)
      • Halle, Germany, 06120
        • Universitaetsklinikum Halle - Universitaetsklinik und Poliklinik fuer Dermatologie und Venerologie
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, 69120
        • Universitätsklinikum Heidelberg
      • Muenster, Germany, 48149
        • University Hospital Muenster
      • Münster, Germany, 48157
        • Fachklinik Hornheide
      • Nürnberg, Germany, 90419
        • Klinikum Nurnberg Nord
      • Regensburg, Germany, 93053
        • Universitätsklinikum Regensburg
    • Baden-württemberg
      • Tuebingen, Baden-württemberg, Germany, 72076
        • Universitaetsklinikum Tuebingen
    • Bayern
      • Erlangen, Bayern, Germany, 91054
        • Universitaetsklinikum Erlangen
      • München, Bayern, Germany, 80337
        • Klinik und Poliklinik für Dermatologie und Allergologie
    • Niedersachsen
      • Buxtehude, Niedersachsen, Germany, 21614
        • Elbe Kliniken Stade-Buxtehude, Klinikum Buxtehude
    • Nordrhein-westfalen
      • Bonn, Nordrhein-westfalen, Germany, 53127
        • Universitatsklinikum Bonn
      • Minden, Nordrhein-westfalen, Germany, 32429
        • Johannes Wesling Klinikum Minden
    • Rheinland-pfalz
      • Mainz, Rheinland-pfalz, Germany, 55131
        • Universitätsmedizin Johannes Gutenberg Universität Mainz
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus Dresden
      • Leipzig, Sachsen, Germany, 04103
        • Universitätsklinikum Leipzig
    • Schleswig-holstein
      • Kiel, Schleswig-holstein, Germany, 24105
        • Universitaetsklinikum Schleswig-Holstein Campus Kiel
      • Lübeck, Schleswig-holstein, Germany, 23538
        • Universitätsklinikum Schleswig-Holstein
    • Thüringen
      • Gera, Thüringen, Germany, 07548
        • SRH Wald-Klinikum Gera
  • Greece
    • Attikí
      • Athens, Attikí, Greece, 11527
        • General Hospital of Athens "LAIKO"
      • Athens, Attikí, Greece, 11527
        • Laiko Hospital
      • Piraeus, Attikí, Greece, 185 47
        • Metropolitan Hospital
    • Irakleío
      • Heraklion, Irakleío, Greece, 71500
        • University General Hospital of Heraklion
    • Kentrikí Makedonía
      • Thessaloniki, Kentrikí Makedonía, Greece, 546 22
        • Bioclinic Thessalonikis Private Clinic Single Member S.A.
  • Hungary
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet
      • Budapest, Hungary, 1085
        • Semmelweis Egyetem
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont
      • Szeged, Hungary, 6720
        • Szent-Györgyi Albert Klinikai Központ
      • Szolnok, Hungary, 5004
        • Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház
    • Baranya
      • Pécs, Baranya, Hungary, 7632
        • Pecsi Tudomanyegyetem Klinikai Kozpont
  • Israel
      • Be'er-Sheva, Israel, 8410101
        • Soroka University Medical Center
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center, Beilinson Hospital
      • Tel Hashomer, Israel, 5265601
        • The Chaim Sheba Medical Center
      • Tel-Aviv, Israel, 6423906
        • Tel Aviv Sourasky Medical Center
    • Hatsafon
      • Afula, Hatsafon, Israel, 1834111
        • Ha'emek Medical Center.
  • Italy
      • Bari, Italy, 70124
        • Istituto Tumori Giovanni Paolo II
      • Genova, Italy, 16132
        • IRCCS Ospedale Policlinico San Martino
      • Milano, Italy, 20141
        • Istituto Europeo di Oncologia IRCCS
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto IOV - IRCCS
      • Perugia, Italy, 06132
        • AO di Perugia - Ospedale S. Maria della Misericordia, S.C Oncologia Medica
      • Roma, Italy, 00144
        • Istituto Nazionale Tumori Regina Elena
    • Friuli Venezia Giulia
      • Udine, Friuli Venezia Giulia, Italy, 33100
        • Azienda Sanitaria Universitaria Friuli Centrale
    • MI
      • Milano, MI, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
    • RM
      • Roma, RM, Italy, 00167
        • Istituto Dermopatico dell'Immacolata (IDI-IRCCS)
    • SI
      • Siena, SI, Italy, 53100
        • A.O.U.S. Policlinico "Le Scotte"
    • Torino
      • Candiolo, Torino, Italy, 10060
        • Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
  • Mexico
      • Ciudad de México, Mexico, 01120
        • BRCR Global Mexico - CDMX
      • Puebla, Mexico, 72160
        • El Cielo Medical Center
      • Puebla, Mexico, 72160
        • El Cielo Medical Center RSB, S.C
    • Ciudad DE México
      • Benito Juárez, Ciudad DE México, Mexico, 03810
        • ONCARE Viaducto Napoles
    • Guanajuato
      • León, Guanajuato, Mexico, 37178
        • Preparaciones Oncológicas S.C.
    • Nuevo LEÓN
      • Monterrey, Nuevo LEÓN, Mexico, 64710
        • I Can Oncology Center S.A. de C.V.
  • New Zealand
      • Auckland, New Zealand, 1023
        • Auckland City Hospital
    • Canterbury
      • Christchurch, Canterbury, New Zealand, 8011
        • New Zealand Clinical Research (Christchurch)
    • Manawatu
      • Palmerston North, Manawatu, New Zealand, 4414
        • Palmerston North Hospital
  • Norway
      • Oslo, Norway, 0379
        • Oslo universitetssykehus, Radiumhospitalet
    • Akershus
      • Lørenskog, Akershus, Norway, 1474
        • Akershus Universitetssykehus
  • Poland
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne
      • Krakow, Poland, 30-348
        • Jagiellońskie Centrum Innowacji Sp. z o .o.
      • Krakow, Poland, 31-826
        • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o .o.
      • Poznan, Poland, 60-780
        • Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
      • Warszawa, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
  • Russian Federation
      • Kaliningrad, Russian Federation
        • Ars Medika Center, LLC
      • Omsk, Russian Federation, 644046
        • BIH of Omsk Region "Clinical Oncological Dispensary"
      • St.Petersburg, Russian Federation, 197022
        • Eurocityclinic LLC
    • Saint-petersburg
      • Pushkin, Saint-petersburg, Russian Federation, 196603
        • Private medical institution "Euromedservice"
  • Slovakia
      • Banska Bystrica, Slovakia, 975 17
        • Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
      • Bratislava, Slovakia, 833 10
        • Narodny Onkologicky Ustav
      • Bratislava, Slovakia, 812 50
        • Onkologicky ustav sv. Alzbety, s.r.o.
      • Kosice, Slovakia, 04191
        • Vychodoslovensky onkologicky ustav, a.s.
      • Partizanske, Slovakia, 95801
        • Nemocnica na okraji mesta, n.o.
      • Poprad, Slovakia, 058 01
        • POKO Poprad, s.r.o.
  • South Africa
      • Pretoria, South Africa, 0181
        • Mary Potter Oncology Centre
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2193
        • WITS Clinical Research
      • Johannesburg, Gauteng, South Africa, 2196
        • Sandton Oncology Medical Group (Pty) Ltd
      • Pretoria, Gauteng, South Africa, 0081
        • Drs Alberts, Bouwer and Jordaan Inc.
  • Spain
      • A Coruña, Spain, 15006
        • CHUAC-Hospital Teresa Herrera
      • Barcelona, Spain, 08041
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08036
        • Hospital Clínic Barcelona
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
      • Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofía
      • Jaen, Spain, 23007
        • Complejo Hospitalario de Jaen
      • Lleida, Spain, 25198
        • Hospital Universitario Arnau de Vilanova
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
      • Málaga, Spain, 29011
        • Hospital Regional Universitario de Malaga - Hospital Civil
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46009
        • Fundacion Instituto Valenciano de Oncologia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • A Coruna
      • Santiago De Compostela, A Coruna, Spain, 15706
        • CHUS - Hospital Clinico Universitario
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • ICO-Badalona Hospital Germans Trias i Pujol
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro Majadahonda
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Clínico Universitario Virgen de la Arrixaca
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Complejo Hospitalario de Navarra
  • Switzerland
      • Winterthur, Switzerland, 8401
        • Kantonsspital Winterthur
      • Zürich Flughafen, Switzerland, 8058
        • Universitätsspital Zürich
  • Turkey
      • Ankara, Turkey, 06520
        • Memorial Ankara Hastanesi
      • Ankara, Turkey, 06800
        • Ankara Sehir Hastanesi
    • İ̇stanbul
      • Istanbul, İ̇stanbul, Turkey, 34098
        • Istanbul University Cerrahpasa Medical Faculty Hospital
      • Istanbul, İ̇stanbul, Turkey, 34722
        • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
      • İstanbul, İ̇stanbul, Turkey, 34214
        • Medipol Mega Universite Hastanesi
  • Ukraine
      • Dnipro, Ukraine, 49102
        • Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
      • Khmelnytskyi, Ukraine, 29009
        • Municipal non-profit enterprise Khmelnytsky regional antitumor center of Khmelnytsky regional
      • Kyiv, Ukraine, 03022
        • National Cancer Institute
      • Kyiv, Ukraine, 02094
        • Municipal non-profit enterprise "Kyiv City Clinical Hospital No. 2" of the executive body of the
      • Lviv, Ukraine, 79031
        • Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Oncological Regional Therapeutical
      • M. Kharkiv, Ukraine, 61103
        • Derzhavna ustanova Instytut zahalnoi ta nevidkladnoi khirurhii im.V.T.Zaitseva Natsionalnoi akademii
      • M. Kharkiv, Ukraine, 61166
        • Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovany
      • Zaporizhzhia, Ukraine, 69040
        • Municipal non-profit enterprise "Zaporizhzhia Regional Antitumor Center" Zaporizhzhya Regional Counc
    • KYIV Region, Obukhiv District
      • Pliuty Village, KYIV Region, Obukhiv District, Ukraine, 08720
        • Medical and diagnostic center of MedX-Ray International Group Limited Liability Company Israeli
  • United Kingdom
      • London, United Kingdom, EC1A 7BE
        • St. Bartholomew's Hospital, Barts Health NHS Trust
      • Nottingham, United Kingdom, NG5 1PB
        • Nottingham University Hospitals NHS Trust
      • Swansea, United Kingdom, SA2 8QA
        • The South West Wales Cancer Institute, Swansea Bay University Health Board
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
        • Nottingham University Hospitals NHS Trust
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Hematology/Oncology - Westwood (Building 100)
      • Los Angeles, California, United States, 90024
        • UCLA - Hematology/Oncology - Administrative Office
      • Los Angeles, California, United States, 90095
        • Ronald Reagan UCLA Medical Center Drug Information Center , Dept. of Pharmaceutical Services (Drug
      • Los Angeles, California, United States, 90095
        • Ronald Reagan UCLA Medical Center, Drug Information Center, Dept. of Pharmaceutical Services (Main O
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver CTO/CTRC
      • Aurora, Colorado, United States, 80045
        • UCHealth Sue Anschutz-Rodgers Eye Center
    • Florida
      • Cape Coral, Florida, United States, 33909
        • Florida Cancer Specialists
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists
      • Orlando, Florida, United States, 32804
        • AdventHealth Orlando Infusion Center
      • Orlando, Florida, United States, 32804
        • AdventHealth Orlando
      • Orlando, Florida, United States, 32804
        • AdventHealth Orlando, Investigational Drug Services
    • Illinois
      • Park Ridge, Illinois, United States, 60068
        • Advocate Medical Group-Park Ridge, Luther Lane-Oncology
    • Kansas
      • Westwood, Kansas, United States, 66205
        • The University of Kansas Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02114
        • Ophthalmic Consultants of Boston Inc (OCB)
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Revive Research Institute, Inc.
      • Farmington Hills, Michigan, United States, 48344
        • Michigan Health Professionals
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Frontier Cancer Center
      • Billings, Montana, United States, 59101
        • St. Vincent Healthcare
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Medical Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
    • Texas
      • Carrollton, Texas, United States, 75010
        • Texas Oncology - Carrollton
      • Flower Mound, Texas, United States, 75028
        • Texas Oncology - Flower Mound
      • Flower Mound, Texas, United States, 75028
        • North Dallas Eye Associates
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine Medical Center
      • Houston, Texas, United States, 77054
        • Harris Health System - Smith Clinic
      • Houston, Texas, United States, 77030
        • CHI St. Luke's Health Baylor College of Medicine Medical Center
      • Houston, Texas, United States, 77030
        • Baylor Clinic
      • Houston, Texas, United States, 77030
        • Harris Health System - Ben Taub Hospital
      • Paris, Texas, United States, 75460
        • Texas Oncology-Paris
      • Paris, Texas, United States, 75460
        • Dan Brown O.D.
      • Temple, Texas, United States, 76508
        • Baylor Scott & White Medical Center - Temple
    • Utah
      • American Fork, Utah, United States, 84003
        • Utah Cancer Specialists
      • Bountiful, Utah, United States, 84010
        • Utah Cancer Specialists
      • Layton, Utah, United States, 84041
        • Utah Cancer Specialists
      • Murray, Utah, United States, 84157
        • Utah Cancer Specialists
      • Ogden, Utah, United States, 84405
        • Utah Cancer Specialists
      • Provo, Utah, United States, 84604
        • Utah Cancer Specialists
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists
      • Salt Lake City, Utah, United States, 84102
        • Utah Cancer Specialists
      • West Jordan, Utah, United States, 84088
        • Utah Cancer Specialists
      • West Valley City, Utah, United States, 84119
        • Utah Cancer Specialists

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Exclusion Criteria

  • 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). 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Triplet Arm
Encorafenib and Binimetinib in combination with Pembrolizumab
Drug: Encorafenib
Encorafenib
Other Names:
  • BRAFTOVI
Drug: Binimetinib
Binimetinib
Other Names:
  • MEKTOVI
Drug: Pembrolizumab
Pembrolizumab
Other Names:
  • KEYTRUDA
Active Comparator: Control Arm
Pembrolizumab
Drug: Pembrolizumab
Pembrolizumab
Other Names:
  • KEYTRUDA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Lead In (SLI): Incidence of Dose Limiting Toxicities (DLTs)
Time Frame: First 2 Cycles of Treatment (cycles are 21 days)
A DLT is defined as any adverse event or laboratory value that is assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring within the first 2 cycles of treatment.
First 2 Cycles of Treatment (cycles are 21 days)
Phase 3: Objective Response (OR) by Blinded Independent Central Review (BICR)
Time Frame: Time from the date of randomization until documented PD, start of subsequent anticancer therapy, or death due to any cause (approximately every 9 weeks).
OR is defined as confirmed Best Overall response (BOR) of either CR or PR as determined by BICR assessment per RECIST 1.1
Time from the date of randomization until documented PD, start of subsequent anticancer therapy, or death due to any cause (approximately every 9 weeks).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Lead in (SLI) and Phase 3: Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments.
Time Frame: Time from first dose of study intervention through 28 days after the last dose of study intervention.
AEs, laboratory parameters, vital signs and cardiac abnormalities will be graded according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 4.03).
Time from first dose of study intervention through 28 days after the last dose of study intervention.
Phase 3: Overall Survival (OS)
Time Frame: Time from the date of randomization to the date of death due to any cause.
OS is defined as the time from the date of randomization to the date of death due to any cause
Time from the date of randomization to the date of death due to any cause.
Phase 3: Duration of Response (DOR)
Time Frame: Time from date of first documented response (CR or PR) to the date of first documented disease progression, as determined by BICR and investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)
DOR is defined as the time from the date of first documented response to the date of first documented disease progression, as determined by BICR and investigator assessment or death due to any cause, whichever occurs first.
Time from date of first documented response (CR or PR) to the date of first documented disease progression, as determined by BICR and investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)
Safety Lead in (SLI): Plasma concentration-time profiles and Pharmacokinetic (PK) parameter estimates for encorafenib and binimetinib.
Time Frame: Cycle 2, Day 1
To measure plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)
Cycle 2, Day 1
Phase 3: Plasma concentrations of encorafenib and binimetinib.
Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 (Each Cycle is 21 days)
To measure the plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)
Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 (Each Cycle is 21 days)
Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30): change from baseline in the global health status/QoL score.
Time Frame: Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
EORTC QLQ-30 includes 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/Quality of Life scale
Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
Phase 3: Change from baseline in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale score.
Time Frame: Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
The FACT-M is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, melanoma-specific items, and items related to melanoma surgery
Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
Phase 3: Change from baseline in 5-level EuroQol-5D (EQ-5D-5L) index score and visual analog scale (VAS)
Time Frame: Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
The EQ-5D-5L is a standardized measure of health utility that provides a single index value of health status and contains 1 item for each of 5 dimensions of HRQoL (ie, mobility, self-care, usual activities, pain or discomfort, and anxiety or depression).
Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
Phase 3: Change from baseline in Patient Global Impression of Severity (PGIS) score
Time Frame: Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".
Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
Phase 3: Patient Global Impression of Change (PGIC) score
Time Frame: Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"
Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months
Safety Lead in (SLI) and Phase 3: Time to Response (TTR)
Time Frame: Time from the date of randomization to the date of first documented response (CR or PR), as determined by investigator assessment per RECIST v1 (approximately every 9 weeks)
TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR), as determined by BICR and investigator or assessment per RECIST v1.1.
Time from the date of randomization to the date of first documented response (CR or PR), as determined by investigator assessment per RECIST v1 (approximately every 9 weeks)
Safety Lead in (SLI) and Phase 3: Objective Response (OR)
Time Frame: Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks).
OR is defined as confirmed Best Overall Response (BOR) of either CR or PR as determined by investigator assessment per RECIST v1.1
Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks).
Safety Lead in (SLI) and Phase 3: Disease Control (DC)
Time Frame: Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks)
DC is defined as confirmed BOR of CR, PR or SD, as determined by BICR and investigator assessment per RECIST v1.1.
Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks)
Safety Lead In (SLI) and Phase 3: Progression Free Survival (PFS) by Investigator and BICR assessment
Time Frame: The time from the date of randomization to the date of first documented disease progression, as determined by investigator and BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)
PFS by investigator is defined as the time from the date of randomization to the first date of documented disease progression as determined by investigator and BICR assessment per RECIST 1.1 or death due to any cause, whichever occurs first.
The time from the date of randomization to the date of first documented disease progression, as determined by investigator and BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2021

Primary Completion (Estimated)

May 1, 2025

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

December 1, 2020

First Submitted That Met QC Criteria

December 1, 2020

First Posted (Actual)

December 8, 2020

Study Record Updates

Last Update Posted (Estimated)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 12, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C4221016
  • STARBOARD (Other Identifier: Alias Study Number)
  • 2020-004850-31 (EudraCT Number)
  • KEYNOTE-B80 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma

Clinical Trials on Encorafenib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Arab Emirates

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe