A Study Comparing 3 Study Medicines (Encorafenib, Binimetinib, Pembrolizumab) to 2 Study Medicines (Ipilimumab and Nivolumab) in Patients With Advanced Melanoma
NCT ID: NCT05926960
Last Updated: 2025-12-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
38 participants
INTERVENTIONAL
2023-06-13
2026-01-19
Brief Summary
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Melanoma is a type of cancer that starts in the cells that give color to your skin.
The study is seeking participants who:
* have advanced or metastatic melanoma (has spread to other parts of the body);
* have a certain abnormal gene called "BRAF".
* have taken nivolumab or pembrolizumab treatment before this study.
Participants will either receive:
* pembrolizumab given by intravenous infusion (directly into a vein) every 3 weeks at the study clinic. Participants will also receive encorafenib and binimetinib by mouth every day at home,
* or will receive ipilimumab and nivolumab given by intravenous infusion (directly into a vein) every 3 weeks at the study clinic 4 times. This will be followed by nivolumab given by intravenous infusion every 4 weeks at the study clinic.
Both pembrolizumab and nivolumab will be given for a maximum of around 2 years. However, there is no time limit for encorafenib and binimetinib treatment.
The study team will see how each participant is doing after receiving the study treatments during regular visits to the study clinic.
Detailed Description
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Approximately 150 participants will be randomized in a 1:1 ratio to the triplet or the doublet/control therapy (75 participants in each arm). Randomization will be stratified by baseline serum LDH level, and by type of PD-1 resistance.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Triplet
encorafenib and binimetinib in combination with pembrolizumab
encorafenib
encorafenib
binimetinib
binimetinib
pembrolizumab
pembrolizumab
Doublet
ipilimumab and nivolumab
ipilimumab
ipilimumab
nivolumab
nivolumab
Interventions
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encorafenib
encorafenib
binimetinib
binimetinib
pembrolizumab
pembrolizumab
ipilimumab
ipilimumab
nivolumab
nivolumab
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
* Documented evidence of a BRAF V600E or V600K mutation.
* Availability of adequate tumor tissue (archival or newly obtained; block or slides) to submit to the sponsor central laboratory(ies) during the screening period for central biomarker analyses .
* Must have received only 1 prior line of systemic therapy for melanoma (either adjuvant therapy or first-line anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab)
* Must have anti-PD-1 resistant disease (primary or secondary) with confirmed disease progression per RECIST v1.1 either during or after receipt of an approved anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab) for melanoma, defined according to the SITC Immunotherapy Resistance Taskforce (Kluger et al, 2020).
* Have at least one measurable lesion per RECIST v1.1.
* ECOG PS of 0-1, and adequate organ and cardiac function, including LVEF ≥50% by cardiac imaging.
Exclusion Criteria
* Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment with chronic systemic steroid therapy or any other form of immunosuppressive therapy within the past 2 years.
* Clinically significant cardiovascular diseases.
* History of thromboembolic or cerebrovascular events ≤12 weeks prior to randomization.
* History or current evidence of RVO or current risk factors for RVO.
* Concurrent neuromuscular disorder that is associated with the potential of elevated CK.
* Active bacterial, fungal, or viral infection requiring systemic therapeutic treatment within 2 weeks prior to randomization.
* Current non-infectious pneumonitis/interstitial lung disease or history of noninfectious pneumonitis/interstitial lung disease requiring steroids.
* Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
* Participants who permanently discontinued prior anti-PD-1 therapy due to toxicity or will be unable to tolerate combination therapy based on investigator judgement are excluded.
* Prior treatment with ipilimumab; prior combined immunotherapy blockade with anti-PD-1/L-1; prior treatment with a BRAFi and/or MEKi; or previous administration of an investigational anti-cancer agent for the adjuvant or first-line treatment of melanoma prior to randomization.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
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Universitaetsklinikum Tuebingen
Tübingen, Baden-Wurttemberg, Germany
Medizinische Hochschule Hannover
Hanover, Lower Saxony, Germany
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, Germany
Fachklinik Hornheide
Münster, North Rhine-Westphalia, Germany
Universitätsmedizin Johannes Gutenberg Universität Mainz
Mainz, Rhineland-Palatinate, Germany
Universitätsklinikum Schleswig-Holstein
Lübeck, Schleswig-Holstein, Germany
Istituto Nazionale Tumori Regina Elena
Rome, ROMA, Italy
A.O.U. Policlinico Paolo Giaccone
Palermo, Sicily, Italy
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
Candiolo, Torino, Italy
Azienda Ospedaliero Universitaria Senese
Siena, Tuscany, Italy
AO Santa Maria della Misericordia
Perugia, Umbria, Italy
Istituto Oncologico Veneto IRCCS
Padua, Veneto, Italy
Istituto Europeo di Oncologia IRCCS
Milan, , Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Napoli, , Italy
Pratia MCM Krakow
Krakow, , Poland
Narodny onkologicky ustav
Bratislava, , Slovakia
Neovizia, s.r.o.
Bratislava, , Slovakia
Hospital Germans Trias i Pujol
Badalona, Barcelona [barcelona], Spain
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], Spain
Institut Català d'Oncologia - L'Hospitalet
L'Hospitalet de Llobregat, Catalunya [cataluña], Spain
Hospital General Universitario de Valencia
Valencia, Valenciana, Comunitat, Spain
Hospital General Universitario Gregorio Marañon
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario Miguel Servet
Zaragoza, , Spain
Countries
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Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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KEYNOTE-C92
Identifier Type: OTHER
Identifier Source: secondary_id
2023-509471-17-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
MK-3475-C92
Identifier Type: OTHER
Identifier Source: secondary_id
C4221023
Identifier Type: -
Identifier Source: org_study_id