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

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: Melanoma
• Intervention / Treatment: Drug: Encorafenib; Drug: Binimetinib; Drug: Pembrolizumab

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): 257
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1426ANZ
      • Instituto Alexander Fleming
  • Río Negro Province
    • Viedma, Río Negro Province, Argentina, 8500
      • Clinica Viedma S. A
• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
• 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
    • Passo Fundo, Rio Grande do Sul, Brazil, 99010-260
      • Hospital de Clínicas de Passo Fundo
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
  • Rio de Janeiro
    • Rio de Janeiro, Rio de Janeiro, Brazil, 20220-410
      • Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Fundação Pio XII - Hospital de Câncer de Barretos
• Bulgaria
  • Plovdiv, Bulgaria, 4004
    • Complex Oncology Center - Plovdiv 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
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • CIUSSS du Saguenay-Lac-Saint-Jean
• Czechia
  • Ostrava-Poruba, Czechia, 708 52
    • Fakultni Nemocnice Ostrava
  • Praha 8-Liben, Czechia, 180 81
    • Fakultni nemocnice Bulovka
  • Olomoucký kraj
    • 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
  • La Tronche, France, 38700
    • CHU Grenoble Alpes
  • Pierre-Bénite, France, 69310
    • Hôpital Lyon Sud
  • Poitiers, France, 86000
    • CHU De Poitiers
• Germany
  • Berlin, Germany, 10117
    • Charité Universitaetsmedizin Berlin - Campus Mitte
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt
  • Essen, Germany, 45147
    • Universitatsklinikum Essen (Aor)
  • Halle, Germany, 06120
    • Universitaetsklinikum Halle - Universitaetsklinik und Poliklinik fuer Dermatologie und Venerologie
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Leipzig, Germany, 04103
    • Zentrum fuer Radiologie und Nuklearmedizin am Johannisplatz
  • Münster, Germany, 48157
    • Fachklinik Hornheide
  • Münster, Germany, 48149
    • University hospital Muenster
  • Nuremberg, Germany, 90419
    • Klinikum Nurnberg Nord
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen
  • Bavaria
    • München, Bavaria, Germany, 80337
      • Klinik und Poliklinik fur Dermatologie und Allergologie
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Universitatsklinikum Bonn
    • Minden, North Rhine-Westphalia, Germany, 32429
      • Johannes Wesling Klinikum Minden
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitätsmedizin Johannes Gutenberg Universität Mainz
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus, Technischen Universitaet Dresden
    • Leipzig, Saxony, Germany, 04103
      • Universitatsklinikum Leipzig
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein Campus Kiel
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitätsklinikum Schleswig-Holstein
  • Thuringia
    • Gera, Thuringia, Germany, 07548
      • SRH Wald-Klinikum Gera
• Greece
  • Attikí
    • Athens, Attikí, Greece, 11527
      • General Hospital of Athens "Laiko"
    • Athens, Attikí, Greece, 11527
      • Laiko Hospital
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Pécs, Hungary
    • University of Pecs, Clinical Center
  • Szeged, Hungary, 6720
    • Szent-Gyorgyi Albert Klinikai Kozpont
  • Baranya
    • Pécs, Baranya, Hungary, 7632
      • Pecsi Tudomanyegyetem Klinikai Kozpont
  • Jász-Nagykun-Szolnok
    • Szolnok, Jász-Nagykun-Szolnok, Hungary, 5004
      • Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház
• Israel
  • Beersheba, Israel, 8410101
    • Soroka university medical center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem
• Italy
  • Bari, Italy, 70124
    • Istituto Tumori Giovanni Paolo II
  • Genova, Italy, 16132
    • IRCCS Azienda Ospedaliera Metropolitana (IRCCS AOM)
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia IRCCS
  • Naples, 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
    • Milan, MI, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Perugia
    • San Sisto, Perugia, Italy, 06132
      • Dipartimento di Medicina e Chirurgia dell' Universita
  • RM
    • Roma, RM, Italy, 00167
      • Istituto Dermopatico dell'Immacolata (IDI-IRCCS)
  • ROMA
    • Rome, ROMA, Italy, 00144
      • Istituti Fisioterapici Ospitalieri
  • 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
  • Guanajuato City, Mexico, 37150
    • Centro de Atencion Integral En Oncologia S.C
  • Mexico City, Mexico, 01120
    • BRCR Global Mexico - CDMX
  • Puebla City, Mexico, 72160
    • El Cielo Medical Center RSB, S.C
  • Querétaro City, Mexico, 76100
    • Boca Clinical Trials Mexico SC
  • Guanajuato
    • León, Guanajuato, Mexico, 37178
      • Preparaciones Oncológicas S.C.
  • Mexico City
    • Benito Juárez, Mexico City, Mexico, 03810
      • ONCARE Viaducto Napoles
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64710
      • I Can Oncology Center S.A. de C.V.
• New Zealand
  • Manawatu
    • Palmerston North, Manawatu, New Zealand, 4414
      • Palmerston North Hospital
• Norway
  • Oslo, Norway, 0379
    • Oslo universitetssykehus, Radiumhospitalet
• Poland
  • Krakow, Poland, 30-348
    • Jagiellońskie Centrum Innowacji Sp. z o .o.
  • Poznan, Poland, 60-780
    • Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
• Russia
  • Kaliningrad, Russia, 236006
    • Ars Medika Center, LLC
  • Omsk, Russia, 644046
    • BIH of Omsk Region "Clinical Oncological Dispensary"
  • Saint Petersburg, Russia, 197022
    • Eurocityclinic LLC
  • Sankt-Peterburg
    • Pushkin, Sankt-Peterburg, Russia, 196603
      • Private Medical Institution "Euromedservice"
• Slovakia
  • Bratislava, Slovakia, 833 10
    • Narodny Onkologicky Ustav
  • Bratislava, Slovakia, 812 50
    • Onkologicky ustav sv. Alzbety, s.r.o.
  • Košice, Slovakia, 04191
    • Vychodoslovensky onkologicky ustav, a.s.
  • Partizánske, Slovakia, 95801
    • Nemocnica na okraji mesta, n.o.
  • Poprad, Slovakia, 058 01
    • POKO Poprad, s.r.o.
• South Africa
  • Pretoria, South Africa
    • Drs Alberts Bouwer Jordaan
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Wits Clinical Research
    • Johannesburg, Gauteng, South Africa, 2193
      • WCR Office
    • 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 Clinic Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Jaén, Spain, 23007
    • Complejo Hospitalario de Jaen
  • Lleida, Spain, 25198
    • Hospital Universitario Arnau de Vilanova
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Málaga, Spain, 29011
    • Hospital Regional Universitario de Malaga - Hospital Civil
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46009
    • Fundación Instituto Valenciano de Oncología
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • ICO-Badalona Hospital Germans Trias i Pujol
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Clinico Universitario Virgen de la Arrixaca
• Switzerland
  • Zürich Flughafen, Switzerland, 8058
    • Universitatsspital Zurich
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06520
    • Memorial Ankara Hastanesi
  • İ̇stanbul
    • Istanbul, İ̇stanbul, Turkey (Türkiye), 34722
      • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
    • Istanbul, İ̇stanbul, Turkey (Türkiye), 34098
      • Istanbul University Cerrahpasa Medical Faculty Hospital
• Ukraine
  • Kharkiv, Ukraine, 61166
    • CNI KRC "Regional Cardiology Centre"
  • Kyiv, Ukraine, 03022
    • National Cancer Institute
  • 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
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St. Bartholomew's Hospital, Barts Health NHS Trust
  • London, United Kingdom, E1 1FR
    • Barts Health NHS Trust.
  • Swansea, United Kingdom, SA2 8QA
    • The South West Wales Cancer Institute, Swansea Bay University Health Board
• United States
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth Hematology and Oncology
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando Infusion Center
    • Orlando, Florida, United States, 32803
      • Adventist Health System/Sunbelt, Inc.
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando, Investigational Drug Services
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Clinical Research Center
    • Overland Park, Kansas, United States, 66210
      • The University of Kansas Cancer Center - Overland Park
    • Prairie Village, Kansas, United States, 66208
      • KU Eye Center
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center - Investigational Drug Services
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston Inc (OCB)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • West Chester, Ohio, United States, 45069
      • West Chester Hospital
    • 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

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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)	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)	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.	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)	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)	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.	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.	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.	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.	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)	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	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	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)	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)	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)	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	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

• Sponsor: Pfizer
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Actual): January 12, 2026
• Study Completion (Estimated): August 31, 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 (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Skin Cancer; Melanoma; BRAF; BRAF V600E/K Melanoma; Advanced Melanoma; Metastatic Melanoma; Advanced Skin Cancer; Starboard; Stage 3 Melanoma; Stage 4 Melanoma; BRAF Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin and Connective Tissue Diseases; Melanoma; Skin Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; encorafenib; binimetinib
• Other Study ID Numbers: C4221016; 2024-512038-13-00 (Registry Identifier: CTIS (EU)); KEYNOTE-B80; STARBOARD (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