En undersøgelse af Encorafenib Plus Cetuximab med eller uden kemoterapi hos mennesker med tidligere ubehandlet metastatisk kolorektal cancer
15. maj 2026 opdateret af: Pfizer
ET ÅBEN-LABEL, MULTICENTER, RANDOMISERET FASE 3-STUDIE AF FØRSTE-LINE ENCORAFENIB PLUS CETUXIMAB MED ELLER UDEN KEMOTERAPI VERSUS STANDARD FOR PLEJEBEHANDLING MED EN SIKKERHEDSLEAD-IN AF ENCORAFENIB PLUS CETUXIMAB MED ELLER UDEN KEMOTERAPI VERSUS STANDARD FOR PLEJEBEHANDLING MED EN SIKKERHEDSINDLEDNING AF ENCORAFENIB PLUS CETUXIMABY 6
Formålet med denne undersøgelse er at evaluere to undersøgelseslægemidler (encorafenib plus cetuximab) taget alene eller sammen med standard kemoterapi til den potentielle behandling af kolorektal cancer, der:
- har spredt sig til andre dele af kroppen (metastatisk);
- har en bestemt type unormalt gen kaldet "BRAF"; og
- ikke har modtaget forudgående behandling.
Deltagere i denne undersøgelse vil modtage en af følgende undersøgelsesbehandlinger:
- Encorafenib plus cetuximab: Disse deltagere vil modtage encorafenib gennem munden derhjemme hver dag og cetuximab en gang hver anden uge ved intravenøs (IV) infusion (en injektion i venen) på undersøgelsesklinikken.
- Encorafenib plus cetuximab med kemoterapi: Disse deltagere vil modtage encorafenib og cetuximab på den måde, der er beskrevet i punkten ovenfor. Derudover vil de modtage standard kemoterapi ved IV-infusion og oral behandling derhjemme.
- Kemoterapi alene: Disse deltagere vil modtage kemoterapi, standardbehandlingen for denne tilstand, ved IV-infusion på undersøgelsesklinikkerne og oral behandling i hjemmet.
Undersøgelsesteamet vil overvåge, hvordan hver deltager reagerer på undersøgelsesbehandlingen i op til omkring 3 år.
Studieoversigt
Status
Aktiv, ikke rekrutterende
Betingelser
Detaljeret beskrivelse
Formålet med undersøgelsen er at evaluere, om encorafenib plus cetuximab (EC), alene eller i kombination med kemoterapi, kan forbedre kliniske resultater i forhold til nuværende standard kemoterapi hos deltagere med tidligere ubehandlet BRAF V600E-mutant mCRC.
Da encorafenib ikke tidligere er blevet kombineret med kemoterapi, vil tolerabiliteten og PK af EC i kombination med mFOLFOX6 og i kombination med FOLFIRI blive evalueret i separate kohorter i sikkerhedsindledningsdelen af forsøget for at identificere, hvilken kemoterapikombination der skal bruges i fase 3-delen af undersøgelsen.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
841
Fase
- Fase 3
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Buenos Aires, Argentina, 1426
- Instituto Medico Especializado Alexander Fleming
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Córdoba, Argentina, X5004FHP
- Clínica Universitaria Reina Fabiola
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Córdoba, Argentina, X5016KEH
- Hospital Privado Centro Medico de Cordoba
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Tucumán Province
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San Miguel de Tucumán, Tucumán Province, Argentina, 4000
- Centro Medico San Roque
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New South Wales
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Camperdown, New South Wales, Australien, 2050
- Chris O'Brien Lifehouse
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Liverpool, New South Wales, Australien, 2170
- Liverpool Hospital
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St Leonards, New South Wales, Australien, 2065
- GenesisCare North Shore
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St Leonards, New South Wales, Australien, 2065
- GenesisCare - North Shore
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Queensland
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Herston, Queensland, Australien, 4029
- Royal Brisbane and Women's Hospital
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Woolloongabba, Queensland, Australien, 4102
- Princess Alexandra Hospital
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South Australia
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Adelaide, South Australia, Australien, 5011
- The Queen Elizabeth Hospital
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Adelaide, South Australia, Australien, 5000
- Central Adelaide Local Health Network Incorporated
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Victoria
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Clayton, Victoria, Australien, 3168
- Monash Health
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Heidelberg, Victoria, Australien, 3084
- Austin Health
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Melbourne, Victoria, Australien, 3000
- Peter MacCallum Cancer Centre
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Melbourne, Victoria, Australien, 3004
- Alfred Health
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Antwerp, Belgien, 2020
- ZNA Middelheim
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Leuven, Belgien, 3000
- UZ Leuven
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Liège, Belgien, 4000
- Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
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Wilrijk, Belgien, 2610
- ZAS Augustinus
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Bruxelles-capitale, Région de
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Brussels, Bruxelles-capitale, Région de, Belgien, 1070
- Université Libre de Bruxelles - Hôpital Erasme
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Brussels, Bruxelles-capitale, Région de, Belgien, 1200
- Cliniques universitaires Saint-Luc
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Hainaut
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Charleroi, Hainaut, Belgien, 6060
- Grand Hôpital de Charleroi
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West-vlaanderen
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Kortrijk, West-vlaanderen, Belgien, 8500
- AZ Groeninge Campus Kennedylaan
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brasilien, 90035-903
- Hospital de Clinicas de Porto Alegre
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Rio de Janeiro
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Rio de Janeiro, Rio de Janeiro, Brasilien, 20230-130
- Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
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Santa Catarina
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Blumenau, Santa Catarina, Brasilien, 89010-340
- Reichow - Centro de Ensino e Pesquisa
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Itajaí, Santa Catarina, Brasilien, 88301-220
- Clinica de Neoplasias Litoral
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São Paulo
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Barretos, São Paulo, Brasilien, 14784400
- Fundacao Pio XII - Hospital de Cancer de Barretos
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Barretos, São Paulo, Brasilien, 14.780-070
- Fundacao Pio XII - Hospital de Cancer de Barretos
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Santo André, São Paulo, Brasilien, 09060-650
- CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
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Santo André, São Paulo, Brasilien, 09060-870
- FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Onco
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São José do Rio Preto, São Paulo, Brasilien, 15090000
- Fundação Faculdade Regional de Medicina de São José do Rio Preto
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Gabrovo, Bulgarien, 5300
- MHAT "Dr. Tota Venkova" AD
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Plovdiv, Bulgarien, 4000
- MHAT Central Onco Hospital OOD
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Plovdiv, Bulgarien, 4004
- Complex Oncology Center - Plovdiv EOOD
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Sofia, Bulgarien, 1303
- Medical Center Nadezhda Clinical EOOD
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Sofia, Bulgarien, 1407
- Acibadem City Clinic MHAT Tokuda
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Sofia, Bulgarien, 1750
- University Multiprofile Hospital for Active Treatment Sofiamed
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Pazardzhik
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Panagyurishte, Pazardzhik, Bulgarien, 4500
- MHAT Uni Hospital OOD
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Alberta
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Calgary, Alberta, Canada, T2N 4N2
- Alberta Health Services - Cancer Care, Tom Baker Cancer Centre
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Calgary, Alberta, Canada, T3N 4N1
- Arthur J.E. Child Comprehensive Cancer Centre
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Edmonton, Alberta, Canada, T6G 1Z2
- Cross Cancer Institute
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Edmonton, Alberta, Canada, T6G 2C8
- Alberta Health Services and The Governors of The University of Alberta
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Ontario
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London, Ontario, Canada, N6A 5W9
- London Regional Cancer Program, London Health Sciences Centre
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Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre
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Quebec
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Montreal, Quebec, Canada, H3T 1E2
- Jewish General Hospital
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-
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Copenhagen, Danmark, 2100
- Rigshospitalet
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Herlev, Danmark, 2730
- Herlev and Gentofte Hospital
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Odense C, Danmark, 5000
- Odense University Hospital
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North Denmark
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Aalborg, North Denmark, Danmark, 9000
- Aalborg Universitetshospital, Syd
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Region Syddanmark
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Vejle, Region Syddanmark, Danmark, 7100
- Vejle Sygehus
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Vejle, Region Syddanmark, Danmark, 7100
- Vejle Hospital-Sygehus Lillebaelt
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Birmingham, Det Forenede Kongerige, B9 5SS
- Heartlands Hospital
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London, Det Forenede Kongerige, W12 0HS
- Hammersmith Hospital, Imperial College Healthcare NHS Trust
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London, Det Forenede Kongerige, W6 8RF
- Hammersmith Hospital
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Oxford, Det Forenede Kongerige, OX3 7LE
- Churchill Hospital - Oncology
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HIGH Heaton
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Newcastle upon Tyne, HIGH Heaton, Det Forenede Kongerige, NE7 7DN
- Freeman Hospital
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Surrey
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Sutton, Surrey, Det Forenede Kongerige, SM2 5PT
- Royal Marsden NHS Foundation Trust
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Oulu, Finland, 90220
- Oulu University Hospital
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Pori, Finland, 28500
- Satakunnan Keskussairaala
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Tampere, Finland, 33521
- Tampereen yliopistollinen sairaala
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Tampere, Finland, 33520
- Tampereen yliopistollinen sairaala
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Turku, Finland, 20520
- Turku University Hospital
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Southwest Finland
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Turku, Southwest Finland, Finland, 20520
- Turku University Hospital
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Uusimaa
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Helsinki, Uusimaa, Finland, 00290
- Helsinki University Central Hospital
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Helsinki, Uusimaa, Finland, 00180
- Docrates Syöpäsairaala
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Arizona
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Phoenix, Arizona, Forenede Stater, 85054
- Mayo Clinic Hospital
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Scottsdale, Arizona, Forenede Stater, 85259
- Mayo Clinic in Arizona - Scottsdale
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California
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Los Angeles, California, Forenede Stater, 90033
- USC / Norris Comprehensive Cancer Center
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Los Angeles, California, Forenede Stater, 90033
- USC/Norris Comprehensive Cancer Center
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Los Angeles, California, Forenede Stater, 90033
- Keck Hospital of USC
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Los Angeles, California, Forenede Stater, 90033
- LAC & USC Medical Center
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Los Angeles, California, Forenede Stater, 90033
- USC/Norris Comprehensive Cancer Center/Investigational Drug Services
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Pasadena, California, Forenede Stater, 91105
- Keck Hospital of USC Pasadena
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Florida
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Aventura, Florida, Forenede Stater, 33180
- Mount Sinai Comprehensive Cancer Center, Aventura
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Miami Beach, Florida, Forenede Stater, 33140
- Mount Sinai Medical Center
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Miami Beach, Florida, Forenede Stater, 33140
- Mount Sinai Comprehensive Cancer Center
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Plantation, Florida, Forenede Stater, 33322
- BRCR Medical Center Inc.
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Plantation, Florida, Forenede Stater, 33322
- BRCR Global
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Illinois
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Chicago, Illinois, Forenede Stater, 60637
- University Of Chicago Medical Center
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Chicago, Illinois, Forenede Stater, 60611
- UChicago Medicine - River East
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Flossmoor, Illinois, Forenede Stater, 60422
- UChicago Medicine at Ingalls - Flossmoor
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Harvey, Illinois, Forenede Stater, 60426
- UChicago Medicine Ingalls Memorial
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New Lenox, Illinois, Forenede Stater, 60451
- University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
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Orland Park, Illinois, Forenede Stater, 60462
- The University of Chicago Medicine Center for Advanced Care Orland Park
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Tinley Park, Illinois, Forenede Stater, 60477
- UChicago Medicine at Ingalls - Tinley Park
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Louisiana
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New Orleans, Louisiana, Forenede Stater, 70121
- Ochsner Clinic Foundation
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic Rochester
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Missouri
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City of Saint Peters, Missouri, Forenede Stater, 63376
- Siteman Cancer Center - St Peters
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Creve Coeur, Missouri, Forenede Stater, 63141
- Siteman Cancer Center - West County
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Florissant, Missouri, Forenede Stater, 63031
- Siteman Cancer Center - North County
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St Louis, Missouri, Forenede Stater, 63110
- Washington University School of Medicine
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St Louis, Missouri, Forenede Stater, 63129
- Siteman Cancer Center - South County
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St Louis, Missouri, Forenede Stater, 63110
- Barnes- Jewish Hospital
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Nebraska
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Omaha, Nebraska, Forenede Stater, 68130
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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Omaha, Nebraska, Forenede Stater, 68124
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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Omaha, Nebraska, Forenede Stater, 68114
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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Papillion, Nebraska, Forenede Stater, 68046
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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New Jersey
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Basking Ridge, New Jersey, Forenede Stater, 07920
- Memorial Sloan Kettering Cancer Center - Basking Ridge
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Berkeley Heights, New Jersey, Forenede Stater, 07922
- Summit Medical Group
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Florham Park, New Jersey, Forenede Stater, 07932
- Summit Medical Group
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Middletown, New Jersey, Forenede Stater, 07748
- Memorial Sloan Kettering Cancer Center- Monmouth
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Montvale, New Jersey, Forenede Stater, 07645
- Memorial Sloan Kettering Cancer Center- Bergen
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New York
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Commack, New York, Forenede Stater, 11725
- Memorial Sloan Kettering Cancer Center Commack
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Harrison, New York, Forenede Stater, 10604
- Memorial Sloan Kettering Cancer Center - Westchester
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New York, New York, Forenede Stater, 10022
- Memorial Sloan Kettering Cancer Center
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New York, New York, Forenede Stater, 10065
- Memorial Sloan Kettering Cancer Center - Main Campus
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Uniondale, New York, Forenede Stater, 11553
- Memorial Sloan Kettering Cancer Center- Nassau
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Ohio
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Cleveland, Ohio, Forenede Stater, 44195
- Cleveland Clinic
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Cleveland, Ohio, Forenede Stater, 44195
- Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
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Columbus, Ohio, Forenede Stater, 43221
- Martha Morehouse Medical plaza
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Columbus, Ohio, Forenede Stater, 43210
- The Ohio State University James Cancer Hospital and Solove Research Institute
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Columbus, Ohio, Forenede Stater, 43212
- Stefanie Spielman Comprehensive Breast Cancer
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Columbus, Ohio, Forenede Stater, 43210
- The Ohio State University Wexner Medical Center Investigational Drug Services
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73104
- University of Oklahoma Health Sciences Center, OU Health Stephenson Cancer Center
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Oregon
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Portland, Oregon, Forenede Stater, 97213
- Providence Cancer Institute Franz Clinic
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Portland, Oregon, Forenede Stater, 97213
- Providence Portland Medical Center
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Portland, Oregon, Forenede Stater, 97225
- Providence St Vincent Medical Center
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Portland, Oregon, Forenede Stater, 97225
- Providence Onc and Heme Care Clinic - Westside
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Pennsylvania
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Pittsburgh, Pennsylvania, Forenede Stater, 15232
- UPMC Hillman Cancer Center
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Tennessee
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Germantown, Tennessee, Forenede Stater, 38138
- The West Clinic. PLLC. dba West Cancer Center
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Nashville, Tennessee, Forenede Stater, 37232
- Vanderbilt-Ingram Cancer Center
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Nashville, Tennessee, Forenede Stater, 37232
- Henry-Joyce Cancer Clinic
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Texas
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Houston, Texas, Forenede Stater, 77030
- The University of Texas MD Anderson Cancer Center
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Virginia
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Richmond, Virginia, Forenede Stater, 23219
- Virginia Commonwealth University
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Washington
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Seattle, Washington, Forenede Stater, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, Forenede Stater, 98195
- University of Washington Medical Center
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Wisconsin
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Madison, Wisconsin, Forenede Stater, 53792
- University of Wisconsin Clinical Science Center
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Utrecht, Holland, 3584 CX
- Universitair Medisch Centrum Utrecht
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North Brabant
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Eindhoven, North Brabant, Holland, 5623 EJ
- Catharina Ziekenhuis
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North Holland
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Amsterdam, North Holland, Holland, 1066 CX
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
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Maharashtra
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Mumbai, Maharashtra, Indien, 400012
- Tata Memorial Hospital
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Pune, Maharashtra, Indien, 411 004
- Deenanath Mangeshkar Hospital & Research Centre
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Pune, Maharashtra, Indien, 411 004
- Sahyadri Speciality Hospital
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Thane, Maharashtra, Indien, 401107
- Bhakti Vedanta Hospital and Research Institute
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National Capital Territory of Delhi
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New Delhi, National Capital Territory of Delhi, Indien, 110085
- Rajiv Gandhi Cancer Institute And Research Centre
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Rajasthan
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Jaipur, Rajasthan, Indien, 302004
- Sawai Man Singh Medical College Hospital (SMS Hospital)
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Brescia, Italien, 25124
- Fondazione Poliambulanza Istituto Ospedaliero
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Milan, Italien, 20141
- Istituto Europeo di Oncologia IRCCS
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Naples, Italien, 80131
- Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" di Napoli
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Padova, Italien, 35128
- IRCCS Istituto Oncologico Veneto (IOV)
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Reggio Emilia, Italien, 42123
- Azienda USL - IRCCS di Reggio Emilia - Arcispedale Santa Maria Nuova
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Cagliari
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Monserrato (CA), Cagliari, Italien, 09042
- Azienda Ospedaliera Universitaria di Cagliari - Presidio Policlinico Universitario "D.Casula"
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Foggia
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San Giovanni Rotondo, Foggia, Italien, 71013
- IRCCS Casa Sollievo della Sofferenza
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Milano
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Milan, Milano, Italien, 20162
- ASST Grande Ospedale Metropolitano Niguarda
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Torino
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Candiolo, Torino, Italien, 10060
- Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo IRCCS
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Orbassano, Torino, Italien, 10043
- Azienda Ospedaliero Universitaria San Luigi Gonzaga
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Fukuoka, Japan, 811-1395
- National Hospital Organization Kyushu Cancer Center
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Osaka, Japan, 540-0006
- National Hospital Organization - Osaka National Hospital - Institute For Clinical Research
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Chiba
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Chiba, Chiba, Japan, 260-8717
- Chiba Cancer Center
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Kashiwa, Chiba, Japan, 277-8577
- National Cancer Center Hospital East
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Hokkaido
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Sapporo, Hokkaido, Japan, 060-8648
- Hokkaido University Hospital
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Ishikawa-ken
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Kanazawa, Ishikawa-ken, Japan, 920-8641
- Kanazawa University Hospital
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Kanagawa
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Kawasaki, Kanagawa, Japan, 216-8511
- St. Marianna University Hospital
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Yokohama, Kanagawa, Japan, 2418515
- Kanagawa Cancer Center
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Nagoya, Aichi
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Nagoya, Nagoya, Aichi, Japan, 464-8681
- Aichi Cancer Center Hospital
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Osaka
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Osaka, Osaka, Japan, 5418567
- Osaka Prefectural Hospital Organization Osaka International Cancer Institute
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Sayama, Osaka, Japan, 589-8511
- Kindai University Hospital
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Suita, Osaka, Japan, 565-0871
- Osaka University Hospital
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Takatsuki, Osaka, Japan, 569-8686
- Osaka Medical and Pharmaceutical University Hospital
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Saitama
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Hidaka, Saitama, Japan, 350-1298
- Saitama Medical University International Medical Center
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Ina-machi, Saitama, Japan, 362-0806
- Saitama Prefectural Cancer Center
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Shizuoka
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Nakatogari, Shizuoka, Japan, 411-8777
- Shizuoka Cancer Center
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Tokyo
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Chuo-ku, Tokyo, Japan, 104-0045
- National Cancer Center Hospital
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Koto-ku, Tokyo, Japan, 135-8550
- The Cancer Institute Hospital of JFCR
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Shinjuku-ku, Tokyo, Japan, 160-8582
- Keio University Hospital
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-
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Shanghai, Kina, 201321
- Fudan University Shanghai Cancer Center
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Tianjin, Kina, 300000
- Tianjin Union Medical Center
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Beijing Municipality
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Beijing, Beijing Municipality, Kina, 100142
- Beijing Cancer Hospital
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Beijing, Beijing Municipality, Kina, 100034
- Peking University First Hospital
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Beijing, Beijing Municipality, Kina, 100730
- Beijing Hospital
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Beijing, Beijing Municipality, Kina, 100021
- Cancer Hospital Chinese Academy of Medical Science
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Chongqing Municipality
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Chongqing, Chongqing Municipality, Kina, 400030
- Chongqing University Cancer Hospital
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Fujian
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Fuzhou, Fujian, Kina, 350001
- Fujian Medical University Union Hospital
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Guangdong
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Guangzhou, Guangdong, Kina, 510655
- The Sixth Affiliated Hospital of Sun Yat-sen University
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Guangxi
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Nanning, Guangxi, Kina, 530200
- Affiliated Tumor Hospital of Guangxi Medical University
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Hubei
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Wuhan, Hubei, Kina, 430030
- Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
-
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Hunan
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Changsha, Hunan, Kina, 410013
- The Third XIANGYA Hospital of Central South University
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Changsha, Hunan, Kina, 410011
- The Second Xiangya Hospital of Central South University
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Jiangsu
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Nanjing, Jiangsu, Kina, 210008
- Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
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Liaoning
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Shenyang, Liaoning, Kina, 110022
- Shengjing Hospital of China Medical University
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Shandong
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Jinan, Shandong, Kina, 250117
- Shandong province cancer hospital
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Kina, 200080
- Shanghai General Hospital
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Shanghai, Shanghai Municipality, Kina, 201800
- Ruijin Hospital Shanghai Jiaotong University School of Medicine
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Sichuan
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Chengdu, Sichuan, Kina, 610041
- Sichuan province cancer hospital
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Yunnan
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Kunming, Yunnan, Kina, 650118
- Yunnan Cancer Hospital(The Third Affiliated Hospital of Kunming Medical University)
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Zhejiang
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Hangzhou, Zhejiang, Kina, 310000
- The second Affiliated Hospital of College of Medicine, Zhejiang University
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-
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Oaxaca City, Mexico, 68020
- Centro de Investigacion Clinica de Oaxaca
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Nuevo León
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Monterrey, Nuevo León, Mexico, 64000
- Accelerium, S. de R.L. de C.V.
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Auckland, New Zealand, 1023
- Auckland City Hospital
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-
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Oslo, Norge, 0379
- Oslo universitetssykehus, Radiumhospitalet
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Oslo, Norge, 0450
- Oslo Universitetssykehus Ullevål
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Sør-trøndelag
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Trondheim, Sør-trøndelag, Norge, 7030
- St. Olavs Hospital
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Vest-agder
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Kristiansand, Vest-agder, Norge, N-4615
- Sørlandet Sykehus Kristiansand
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-
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-
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Brzozów, Polen, 36-200
- Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
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Bytom, Polen, 41-902
- Wojewodzki Szpital Specjalistyczny Nr 4 w Bytomiu Oddzial Onkologii
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Gdansk, Polen, 80-219
- Copernicus Podmiot Leczniczy Sp. z o.o. Wojewódzkie Centrum Onkologii
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Gdansk, Polen, 80-219
- COPERNICUS PL sp. z. o. o. Wojewodzkie Centrum Onkologii w Gdansku Ambulatoryjna
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Greater Poland Voivodeship
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Konin, Greater Poland Voivodeship, Polen, 62-500
- Przychodnia Lekarska KOMED
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-
-
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Chelyabinsk, Rusland, 454087
- GBUZ
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Kaluga, Rusland, 248007
- Kaluga Regional Clinical Oncology Center
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Moscow, Rusland, 119991
- FSAEI HE I.M Sechenov First MSMU MoH Russia (Sechenovskiy University),
-
Omsk, Rusland, 644013
- BHI of Omsk region "Clinical Oncology Dispensary"
-
Omsk, Rusland, 644046
- BHI of Omsk region "Clinical Oncology Dispensary"
-
Saint Petersburg, Rusland, 191025
- LLC "Medicina Severnoy Stolitsy"
-
Saint Petersburg, Rusland, 192007
- LLC "Severo-Zapadny Medical Center"
-
Saint Petersburg, Rusland, 195271
- Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg
-
Saint Petersburg, Rusland, 197022
- LLC "Eurocityclinic"
-
Saint Petersburg, Rusland, 197758
- FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov
-
Yaroslavl, Rusland, 150054
- SHI YR Regional Clinical Oncology Hospital
-
-
Sankt-Peterburg
-
Pushkin, Sankt-Peterburg, Rusland, 196603
- Private Medical Institution "Euromedservice"
-
-
-
-
-
Bratislava, Slovakiet, 833 10
- Narodny onkologicky ustav
-
Košice, Slovakiet, 04191
- Vychodoslovensky onkologicky ustav, a.s.
-
-
-
-
-
Barcelona, Spanien, 08035
- Hospital Universitario Vall d'Hebron
-
Barcelona, Spanien, 08036
- Hospital Clinic Barcelona
-
Madrid, Spanien, 28034
- Hospital Universitario Ramon y Cajal
-
Madrid, Spanien, 28041
- Hospital Universitario 12 de Octubre
-
Madrid, Spanien, 28007
- Hospital General Universitario Gregorio Marañón
-
Seville, Spanien, 41013
- Hospital Universitario Virgen del Rocío
-
Valencia, Spanien, 46010
- Hospital Clínico Universitario de Valencia
-
Valencia, Spanien, 46014
- Hospital General Universitario de Valencia
-
Zaragoza, Spanien, 50009
- Hospital Universitario Miguel Servet
-
-
A Coruña
-
Santiago de Compostela, A Coruña, Spanien, 15706
- Complejo Hospitalario Universitario Santiago de Compostela
-
-
Alicante
-
Elche, Alicante, Spanien, 03203
- Hospital General Universitario de Elche
-
-
Barcelona
-
L'Hospitalet de Llobregat, Barcelona, Spanien, 08908
- ICO L'Hospitalet (Hospital Duran i Reynals)
-
-
-
-
-
Stockholm, Sverige, 171 76
- Department of Pelvic cancer, colorecta section, Karolinska University Hospital
-
-
Stockholms LÄN [se-01]
-
Solna, Stockholms LÄN [se-01], Sverige, 171 64
- Karolinska Universitetssjukhuset Solna
-
-
Uppsala LÄN [se-03]
-
Uppsala, Uppsala LÄN [se-03], Sverige, 751 85
- Akademiska Sjukhuset
-
-
Västerbottens LÄN [se-24]
-
Umeå, Västerbottens LÄN [se-24], Sverige, 90185
- Norrlands universitetssjukhus
-
-
Västra Götalands LÄN [se14]
-
Gothenburg, Västra Götalands LÄN [se14], Sverige, 413 45
- Sahlgrenska Universitetssjukhuset
-
-
-
-
-
Johannesburg, Sydafrika, 2193
- Wits Health Consortium (Pty) Ltd
-
-
CAPE TOWN
-
Rondebosch, CAPE TOWN, Sydafrika, 7700
- Cancercare Rondebosch Oncology
-
-
Eastern Cape
-
Port Elizabeth, Eastern Cape, Sydafrika, 6045
- Cancercare Langenhoven Drive Oncology Centre
-
-
-
-
-
Busan, Sydkorea, 49201
- Dong-A University Hospital
-
Daegu, Sydkorea, 41404
- Kyungpook National University Chilgok Hospital
-
Incheon, Sydkorea, 21565
- Gachon University Gil Medical Center
-
Seoul, Sydkorea, 03080
- Seoul National University Hospital
-
Seoul, Sydkorea, 05505
- Asan Medical Center
-
Seoul, Sydkorea, 06351
- Samsung Medical Center
-
Seoul, Sydkorea, 03722
- Severance Hospital, Yonsei University Health System
-
Seoul, Sydkorea, 02841
- Korea University Anam Hospital
-
-
Gyeonggi-do
-
Goyang-si, Gyeonggi-do, Sydkorea, 10408
- National Cancer Center
-
-
-
-
-
Kaohsiung City, Taiwan, 807
- Kaohsiung Medical University Chung-Ho Memorial Hospital
-
Taichung, Taiwan, 404
- China Medical University Hospital
-
Tainan, Taiwan, 704
- National Cheng-Kung University Hospital
-
Tainan, Taiwan, 73657
- Chi Mei Hospital, Liouying
-
Taipei, Taiwan, 100
- National Taiwan University Hospital
-
Taipei, Taiwan, 11031
- Taipei Medical University Hospital
-
Taipei, Taiwan, 112
- Taipei Veterans General Hospital
-
Taoyuan, Taiwan, 333
- Chang Gung Medical Foundation-Linkou Branch
-
-
-
-
-
Olomouc, Tjekkiet, 779 00
- Fakultni Nemocnice Olomouc
-
Prague, Tjekkiet, 180 81
- Fakultní nemocnice Bulovka
-
-
Brno-město
-
Brno, Brno-město, Tjekkiet, 625 00
- Fakultní nemocnice Brno Bohunice
-
-
Hradec Králové
-
Hradec Králové, Hradec Králové, Tjekkiet, 500 05
- Fakultni nemocnice Hradec Kralove
-
-
Praha 4
-
Prague, Praha 4, Tjekkiet, 14059
- Fakultni Thomayerova nemocnice
-
-
-
-
-
Berlin, Tyskland, 10707
- Onkologische Schwerpunktpraxis Kurfuerstendamm
-
Berlin, Tyskland, 13125
- HELIOS Klinikum Berlin Buch GmbH
-
Charlottenburg, Tyskland, 10719
- Radiologie Berlin
-
Dresden, Tyskland, 01307
- Universitätsklinikum Carl Gustav Carus Dresden
-
Dresden, Tyskland, 01307
- Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus
-
Hamburg, Tyskland, 20249
- Facharztzentrum Eppendorf
-
Hamburg, Tyskland, 22045
- ZytoService Deutschland GmbH, Standort-Hamburg-Jenfeld
-
Hamburg, Tyskland, 22297
- Radiologie im Israelitischen Krankenhaus
-
-
Bavaria
-
Munich, Bavaria, Tyskland, 81737
- Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
-
-
Hesse
-
Frankfurt am Main, Hesse, Tyskland, 60488
- Institut für Klinisch Onkologische Forschung
-
-
Lower Saxony
-
Hanover, Lower Saxony, Tyskland, 30625
- Medizinische Hochschule Hannover
-
-
Saxony
-
Leipzig, Saxony, Tyskland, 04103
- Universitatsklinikum Leipzig
-
-
-
-
-
Dnipro, Ukraine, 49102
- Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
-
Ivano-Frankivsk, Ukraine, 76018
- Ivano-Frankivsk National Medical University
-
Ivano-Frankivsk, Ukraine, 76018
- MNPE "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Regional Council"
-
Kryvyi Rih, Ukraine, 50048
- Communal enterprise "Kryvyi Rih Oncology Dispensary" of Dnipropetrovsk Regional Council
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
16 år og ældre (Barn, Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Beskrivelse
Inklusionskriterier:
- Safety Lead-In = Mand/kvinde ≥ 18 år gammel
- Fase 3: Mand/kvinde ≥ 16 år (hvor tilladt lokalt)
- Histologisk eller cytologisk bekræftet Stage IV CRC, der indeholder BRAF V600E mutation
- Forudgående systemisk behandling i metastaserende omgivelser
- SLI: 0-1 kure
- Fase 3: Ingen
- Tidligere adjuverende eller neoadjuverende behandling overvejes metastatisk behandling, hvis tilbagefald/metastaser < 6 måneder fra afslutningen af adj/neoadjuverende behandling
- Målbar sygdom (fase 3)/ Målbar eller evaluerbar sygdom (sikkerhedsindledning)
- ECOG PS 0-1
- Tilstrækkelig organfunktion
Ekskluderingskriterier:
- Tumorer, der er lokalt bekræftede eller ukendte MSI-H eller dMMR, medmindre deltageren ikke er berettiget til at modtage immun checkpoint-hæmmere på grund af en allerede eksisterende medicinsk tilstand
- Aktive bakterielle eller virale infektioner i 2 uger før start af dosering
- Symptomatiske hjernemetastaser
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Sikkerhedsindledende kohorte 1
Encorafenib 300 mg oralt én gang dagligt Cetuximab 500 mg/m2 (120-minutters IV-infusion) hver anden uge Irinotecan 180 mg/m2 (90-minutters IV-infusion) hver anden uge Leucovorin 400 mg/m2 (120-minutters IV-infusion) hver anden uger 5-FU 400 mg/m2 IV bolus, derefter 5-FU 2400 mg/m2 kontinuerlig IV-infusion over 46-48 timer hver anden uge
|
75 mg kapsler
Andre navne:
Injektion til intravenøs brug 100 mg/hætteglas, 200 mg/hætteglas eller 500 mg/hætteglas
Andre navne:
Opløsning til intravenøs infusion 40 mg/hætteglas, 100 mg/hætteglas eller 300 mg/hætteglas
Andre navne:
Injektion 50 mg/hætteglas, 100 mg/hætteglas, 200 mg/hætteglas eller 350 mg/hætteglas
Andre navne:
Injektion til intravenøs brug 250 mg/hætteglas, 500 mg/hætteglas eller 1000 mg/hætteglas
Andre navne:
|
|
Eksperimentel: Sikkerhedsindledende kohorte 2
Encorafenib 300 mg oralt én gang dagligt Cetuximab 500 mg/m2 (120 minutters IV-infusion) hver anden uge Oxaliplatin 85 mg/m2 (120-minutters IV-infusion) hver anden uge Leucovorin 400 mg/m2 (120-minutters IV-infusion) hver anden uge 5-FU 400 mg/m2 IV bolus, derefter 5-FU 2400 mg/m2 kontinuerlig IV-infusion over 46-48 timer hver anden uge
|
75 mg kapsler
Andre navne:
Injektion til intravenøs brug 100 mg/hætteglas, 200 mg/hætteglas eller 500 mg/hætteglas
Andre navne:
Injektion 50 mg/hætteglas, 100 mg/hætteglas, 200 mg/hætteglas eller 350 mg/hætteglas
Andre navne:
Injektion til intravenøs brug 250 mg/hætteglas, 500 mg/hætteglas eller 1000 mg/hætteglas
Andre navne:
Pulver til opløsning til intravenøs brug 50 mg/hætteglas, 100 mg/hætteglas eller 200 mg/hætteglas
Andre navne:
|
|
Eksperimentel: Fase 3 Arm A
Encorafenib 300 mg oralt én gang dagligt Cetuximab 500 mg/m2 (120-minutters IV-infusion) hver anden uge
|
75 mg kapsler
Andre navne:
Injektion til intravenøs brug 100 mg/hætteglas, 200 mg/hætteglas eller 500 mg/hætteglas
Andre navne:
|
|
Eksperimentel: Fase 3 arm B
Encorafenib 300 mg oralt én gang dagligt Cetuximab 500 mg/m2 (120 minutters IV-infusion) hver anden uge Oxaliplatin 85 mg/m2 (120-minutters IV-infusion) hver anden uge Leucovorin 400 mg/m2 (120-minutters IV-infusion) hver anden uge 5-FU 400 mg/m2 IV bolus, derefter 5-FU 2400 mg/m2 kontinuerlig IV-infusion over 46-48 timer hver anden uge
|
75 mg kapsler
Andre navne:
Injektion til intravenøs brug 100 mg/hætteglas, 200 mg/hætteglas eller 500 mg/hætteglas
Andre navne:
Injektion 50 mg/hætteglas, 100 mg/hætteglas, 200 mg/hætteglas eller 350 mg/hætteglas
Andre navne:
Injektion til intravenøs brug 250 mg/hætteglas, 500 mg/hætteglas eller 1000 mg/hætteglas
Andre navne:
Pulver til opløsning til intravenøs brug 50 mg/hætteglas, 100 mg/hætteglas eller 200 mg/hætteglas
Andre navne:
|
|
Aktiv komparator: Fase 3 Arm C
Hver anden uge: Oxaliplatin 85 mg/m2 (120-minutters IV-infusion) Leucovorin 400 mg/m2 (120-minutters IV-infusion) 5-FU 400 mg/m2 IV-bolus, derefter 5-FU 2400 mg/m2 kontinuerlig IV-infusion over 46-48 timer Bevacizumab (valgfrit; givet i henhold til ordinationsinstruktioner) -ELLER- Hver anden uge: Irinotecan 165 mg/m2 (90-minutters IV-infusion) Oxaliplatin 85 mg/m2 (120-minutters IV-infusion) Leucovorin 400 mg/m2 ( 120-minutters IV-infusion) 5-FU 2400 eller 3200 mg/m2 kontinuerlig IV-infusion over 46 48 timer Bevacizumab (valgfrit; givet i henhold til ordinationsinstruktioner) -ELLER- Oxaliplatin 130 mg/m2 (120-minutters IV-infusion) hver 3. uge Capecitabine 1000 mg/m2 oral tablet to gange dagligt på dag 1-14 Bevacizumab (valgfrit; givet i henhold til ordinationsinstruktioner)
|
Opløsning til intravenøs infusion 40 mg/hætteglas, 100 mg/hætteglas eller 300 mg/hætteglas
Andre navne:
Injektion 50 mg/hætteglas, 100 mg/hætteglas, 200 mg/hætteglas eller 350 mg/hætteglas
Andre navne:
Injektion til intravenøs brug 250 mg/hætteglas, 500 mg/hætteglas eller 1000 mg/hætteglas
Andre navne:
Pulver til opløsning til intravenøs brug 50 mg/hætteglas, 100 mg/hætteglas eller 200 mg/hætteglas
Andre navne:
150 mg eller 500 mg tablet
Andre navne:
Valgfri injektion til intravenøs brug 100 mg/hætteglas eller 400 mg/hætteglas
Andre navne:
|
|
Eksperimentel: Kohorte 3 Arm D
Encorafenib 300 mg oralt én gang daglig Cetuximab 500 mg/m2 (120-minutters IV-infusion) hver anden uge Irinotecan 180 mg/m2 (90-minutters IV-infusion) hver anden uge Leucovorin 400 mg/m2 (120-minutters IV-infusion) hver anden uger 5-FU 400 mg/m2 IV bolus, derefter 5-FU 2400 mg/m2 kontinuerlig IV-infusion over 46-48 timer hver anden uge
|
75 mg kapsler
Andre navne:
Injektion til intravenøs brug 100 mg/hætteglas, 200 mg/hætteglas eller 500 mg/hætteglas
Andre navne:
Opløsning til intravenøs infusion 40 mg/hætteglas, 100 mg/hætteglas eller 300 mg/hætteglas
Andre navne:
Injektion 50 mg/hætteglas, 100 mg/hætteglas, 200 mg/hætteglas eller 350 mg/hætteglas
Andre navne:
Injektion til intravenøs brug 250 mg/hætteglas, 500 mg/hætteglas eller 1000 mg/hætteglas
Andre navne:
|
|
Aktiv komparator: Kohorte 3 Arm E
Irinotecan 180 mg/m2 (90-minutters IV-infusion) hver 2. uge, Leucovorin 400 mg/m2 (120-minutters IV-infusion) hver 2. uge, 5-FU 400 mg/m2 IV-bolus, derefter 5-FU 2400 mg/m2 kontinuerlig IV-infusion over 46-48 timer hver anden uge, Bevacizumab (valgfrit; givet i henhold til ordinationsinstruktioner)
|
Opløsning til intravenøs infusion 40 mg/hætteglas, 100 mg/hætteglas eller 300 mg/hætteglas
Andre navne:
Injektion 50 mg/hætteglas, 100 mg/hætteglas, 200 mg/hætteglas eller 350 mg/hætteglas
Andre navne:
Injektion til intravenøs brug 250 mg/hætteglas, 500 mg/hætteglas eller 1000 mg/hætteglas
Andre navne:
Valgfri injektion til intravenøs brug 100 mg/hætteglas eller 400 mg/hætteglas
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
SLI: Number of Participants With Dose Limiting Toxicity (DLTs)
Tidsramme: Cycle 1 (28 days)
|
DLT: Any AE/lab value during first 28 days (D) of treatment that met at least 1 criteria: AE/lab value unrelated to underlying disease,PD,intercurrent illness,concomitant medications resulting in inability to tolerate atleast 75% of planned dose intensity of study drug,fatigue grade (G)3>14 consecutive D, interstitial lung disease G>=2,rash,hand foot skin reaction G3>14 consecutive D or G4,diarrhea G3 >=48 hours or G4,nausea/vomiting G3>=48 hours or G4,mucositis G>=3,total bilirubin G>=3, aspartate aminotransferase/alanine aminotransferase G>=3 in conjunction with total bilirubin G>=2 or G3 >7 consecutive D or G4,Serum creatinine G>=3,absolute neutrophil count G4 >7 consecutive D, >=G3 febrile neutropenia,G3 platelet count decreased with signs of bleeding,platelet count G4,ECG QTcF prolonged >=G3,G>=3 uveitis >21 consecutive D,G4 confirmed by ophthalmic examination,paresthesia/dysesthesias G>=3,other G>=3 hematologic/nonhematologic toxicity except lymphocyte count decreased G>=3.
|
Cycle 1 (28 days)
|
|
Phase 3: Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) for Arm B vs Arm C - FAS
Tidsramme: From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
PFS was defined as the time from date of randomization to earliest documented disease progression (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death due to any cause as assessed by BICR.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 millimeter (mm) for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: Objective Response Rate (ORR) as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset
Tidsramme: From date of randomization to until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 24.71 months)
|
ORR was defined as the percentage of participants who achieved best overall response (BOR) of confirmed complete response (CR) or partial response (PR) according to RECIST v 1.1 as assessed by BICR.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization to until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 24.71 months)
|
|
Cohort 3: ORR as Assessed by BICR for Arm D vs Arm E - FAS
Tidsramme: From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 14.1 months)
|
ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 as assessed by BICR.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 14.1 months)
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
SLI: Number of Participants With Adverse Events (AEs)
Tidsramme: Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
An Serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event.
AEs included both SAEs and all non-SAEs.
|
Through end of the study
|
|
SLI: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
Tidsramme: Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention.
AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
|
Through end of the study
|
|
SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
Tidsramme: Through end of the study
|
The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased.
Laboratory abnormalities were graded according to NCI CTCAE version 4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death.
Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
Tidsramme: Through end of the study
|
The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and lipase increased.
Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening, and grade 5= death related to AE.
Only those chemistry parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
SLI: Number of Participants According to Categorization of Vital Signs Data
Tidsramme: Through end of the study
|
The criteria for vital signs included: Systolic blood pressure (millimeters of mercury [mmHg]): value <= 90 mmHg and decrease from baseline >= 20 mmHg, and value >= 160 mmHg and increase from baseline >= 20 mmHg.
Diastolic blood pressure (mmHg): value <= 50 mmHg and decrease from baseline >= 15 mmHg, and value >= 100 mmHg and increase from baseline >= 15 mmHg.
Pulse rate (beats per minute [bpm]): value <= 50 bpm and decrease from baseline >= 15 bpm, and value >= 120 bpm and increase from baseline >= 15 bpm.
Weight (kilograms [kg]): change >= 20 % decrease from baseline, and change >=10% increase from baseline.
Temperature (degree Celsius): value <=36 degree Celsius, and value >=37.5 degree Celsius.
Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
|
Through end of the study
|
|
SLI: Number of Participants According to Categorization of Electrocardiogram (ECGs) Findings
Tidsramme: Through end of the study
|
ECG criteria included: ECG mean heart rate (beats per minute [bpm]): increase from baseline >25% and to a value >100 bpm; decrease from baseline >25% and to a value <50 bpm, PR interval not otherwise specified (milliseconds [msec]): new >280 msec, QRS interval not otherwise specified (msec): new >120 msec, QT Interval Corrected Using Fridericia's Formula (QTcF) not otherwise specified: new >450 msec; new >480 msec; new >500 msec; increase from baseline >30 msec and increase from baseline >60 msec.
Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
|
Through end of the study
|
|
SLI: Number of Participants With Dose Modification of Any Study Intervention Due to AEs
Tidsramme: Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention.
Dose interruption: for encorafenib = 0 mg dose administered for >=1 days; for cetuximab, oxaliplatin, leucovorin, fluorouracil, irinotecan: >20 days between successive start dates with non-zero actual doses.
Dose reduction: decrease in dose of at least 10%, from the protocol-planned dose and a decrease from the previous non-zero dose; for encorafenib to qualify as a dose reduction, it should have lasted for >=2 days.
Dose modifications included both dose interruptions and reduction.
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Through end of the study
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SLI: Number of Participants With Dose Discontinuation of Any Study Intervention Due to AEs
Tidsramme: Through end of the study
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An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention.
Number of participants with dose discontinuation due to AEs were reported in this outcome measure.
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Through end of the study
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SLI: ORR as Assessed by Investigator According to Line of Therapy - FAS
Tidsramme: From date of randomization until documented PD, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 33.9 months)
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ORR: percentage of participants who achieved BOR of confirmed CR/PR per RECIST v1.1 as assessed by response reported by investigator on eCRF.
CR: complete disappearance of all target lesions (with exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis <10 mm.
PR: >=30% decrease under baseline of sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Percentage of participants with ORR for first line (no prior treatment) and second line (participant received prior treatment viz.
advanced/metastatic or locoregional disease or maintenance or if neoadjuvant/adjuvant with a disease recurrence occurred during or within 6 months of last therapy dose) is presented.
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From date of randomization until documented PD, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 33.9 months)
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SLI: Duration of Response (DOR) as Assessed by Investigator According to Line of Therapy - FAS
Tidsramme: From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause whichever occurred first (maximum up to 33.9 months)
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DOR: time from date of first radiographic evidence of response (CR/PR) to earliest documented PD per RECIST v1.1 as assessed by response reported by investigator on eCRF, or death by any cause.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis <10 mm.
PR: >=30% decrease under baseline of sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
DOR for first line and second line is presented.
Analysis performed by Kaplan Meier method.
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From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause whichever occurred first (maximum up to 33.9 months)
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SLI: PFS as Assessed by Investigator According to Line of Therapy - FAS
Tidsramme: From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 33.9 months)
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PFS: time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by response reported by investigator on eCRF.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Participants with PFS for first line and second line were presented.
Analysis performed using Kaplan Meier method.
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From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 33.9 months)
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SLI: Time to Response (TTR) as Assessed by Investigator According to Line of Therapy - FAS
Tidsramme: From date of first dose to first radiographic evidence of response (CR or PR) (maximum up to 33.9 months [147.3 weeks])
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TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by response reported by investigator on eCRF.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
In this outcome measure, TTR for first line (no prior treatment) and second line (participant received a prior treatment defined as advanced/metastatic or locoregional disease or maintenance or if neoadjuvant/adjuvant with a disease recurrence occurred during or within 6 months of the last dose of therapy) were reported.
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From date of first dose to first radiographic evidence of response (CR or PR) (maximum up to 33.9 months [147.3 weeks])
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SLI: Overall Survival (OS) According to Line of Therapy - FAS
Tidsramme: From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 33.9 months)
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OS was defined as the time from the date of first dose to death due to any cause.
If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact.
In this outcome measure, OS for first line (no prior treatment) and second line (participant received a prior treatment defined as advanced/metastatic or locoregional disease or maintenance or if neoadjuvant/adjuvant with a disease recurrence occurred during or within 6 months of the last dose of therapy) was presented.
Analysis was performed using Kaplan Meier method.
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From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 33.9 months)
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SLI: Maximum Plasma Concentration (Cmax) of Encorafenib and Its Metabolite LHY746
Tidsramme: Cohort 1: Pre-dose (0 hour [hr]), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Cmax was observed directly from data.
LHY746 is a metabolite of Encorafenib.
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Cohort 1: Pre-dose (0 hour [hr]), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI: Area Under the Concentration Time Profile From Time Zero to 6 Hours (AUC6) for Encorafenib and Its Metabolite LHY746
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, and 6 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Predose (0 hr), 1, 2, 3, 4, and 6 hrs post-dose on Days 1 and 15 of Cycle 1
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The AUC was estimated from time 0 to 6 hours post dose.
AUC6 was computed using the Linear/Log trapezoidal method.
LHY746 is a metabolite of Encorafenib.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, and 6 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Predose (0 hr), 1, 2, 3, 4, and 6 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI: Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Encorafenib and Its Metabolite LHY746
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval.
tau = 24 hrs for QD dosing of encorafenib.
LHY746 is a metabolite of encorafenib.
AUCtau can be calculated directly from the data using 24 hrs (tau) sample or can be approximately calculated by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI: Time to Maximum Plasma Concentration (Tmax) of Encorafenib and Its Metabolite LHY746
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Tmax: time (hours) to Cmax.
LHY746 is a metabolite of Encorafenib.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI: Apparent Total Clearance (CL/F) of Encorafenib
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
CL/F was calculated as Dose/AUCinf where dose is the dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf).
AUCinf was calculated as AUClast + (Clast*/kel), where Clast is last plasma concentration from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Day 15 of Cycle 1; Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 1: Cmax of Irinotecan and Its Metabolite SN-38
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Cmax was observed directly from data.
SN-38 is a metabolite of Irinotecan.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 1: AUClast of Irinotecan and Its Metabolite SN-38
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration.
AUClast was calculated using linear/log trapezoidal method.
SN-38 is a metabolite of Irinotecan.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 1: Apparent Terminal Elimination Half-Life (t1/2) of Irinotecan and Its Metabolite SN-38
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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t1/2 was the time measured for the drug concentration to decrease by one half.
t1/2 was determined by Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
SN-38 is a metabolite of Irinotecan.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 1: CL/F of Irinotecan
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf).
AUCinf was calculated as AUClast + (Clast*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 2: Cmax of Oxaliplatin
Tidsramme: Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Cmax was observed directly from data.
Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate.
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Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 2: AUClast of Oxaliplatin
Tidsramme: Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration.
AUClast was calculated using linear/log trapezoidal method.
Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate.
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Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 2: CL/F of Oxaliplatin
Tidsramme: Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf).
AUCinf was calculated as AUClast + (Clast*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
Oxaliplatin consisted of platinum of plasma and platinum in plasma-ultrafiltrate.
The clearance of platinum-ultrafiltrate has been presented in this outcome measure.
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Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 1: Ratio of AUCinf on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Irinotecan and Its Metabolite SN-38
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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AUCinf was calculated as AUClast + (Clast*/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
The ratio between geometric least square (LS) mean (within Cohort 1) for AUCinf on Cycle 1 Day 15 and geometric LS mean (within Cohort 1) for AUCinf on Cycle 1 Day 1 for irinotecan and its metabolite SN-38 has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as "Number".
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 1: Ratio of AUClast on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Irinotecan and Its Metabolite SN-38
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration.
AUClast was calculated using linear/log trapezoidal method.
The ratio between geometric LS mean (within Cohort 1) for AUClast on Cycle 1 Day 15 and geometric LS mean (within Cohort 1) for AUClast on Cycle 1 Day 1 for irinotecan and its metabolite SN-38 has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as "Number".
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 1: Ratio of Cmax on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Irinotecan and Its Metabolite SN-38
Tidsramme: Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Cmax was observed directly from data.
The ratio between geometric LS mean (within Cohort 1) for Cmax on Cycle 1 Day 15 and geometric LS mean (within Cohort 1) for Cmax on Cycle 1 Day 1 for irinotecan and its metabolite SN-38 has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as "Number".
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Cohort 1: Pre-dose (0 hr), 0.75, 1.5, 2.5, 3.5, 5.5, 7.5, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 2: Ratio of AUClast on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Oxaliplatin
Tidsramme: Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration.
AUClast was calculated using linear/log trapezoidal method.
Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate.
The ratio between geometric LS mean (within Cohort 2) for AUClast on Cycle 1 Day 15 and geometric LS mean (within Cohort 2) for AUClast on Cycle 1 Day 1 for Oxaliplatin has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as "Number".
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Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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SLI, Cohort 2: Ratio of Cmax on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Oxaliplatin
Tidsramme: Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Cmax was observed directly from data.
Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate.
The ratio between geometric LS mean (within Cohort 2) for Cmax on Cycle 1 Day 15 and geometric LS mean (within Cohort 2) for Cmax on Cycle 1 Day 1 for Oxaliplatin has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as "Number".
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Cohort 2: Pre-dose (0 hr), 1, 2, 3, 4, 6, 8, and 48 hrs post-dose on Days 1 and 15 of Cycle 1
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Phase 3: OS for Arm B vs Arm C - FAS
Tidsramme: From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
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OS was defined as the time from the date of first dose to death due to any cause.
If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact.
Analysis was performed using Kaplan Meier method.
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From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
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Phase 3: ORR by Derived Investigator Assessment for Arm B vs Arm C - FAS ORR Subset
Tidsramme: From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 24.71 months)
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ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 by derived investigator assessment.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
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From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 24.71 months)
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Phase 3: ORR as Assessed by BICR - FAS
Tidsramme: From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 37.25 months)
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ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 as assessed by BICR.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
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From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 37.25 months)
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Phase 3: DOR as Assessed by BICR for Arm B Versus Arm C - FAS ORR Subset
Tidsramme: From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 24.71 months)
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DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 as assessed by BICR, or death due to any cause.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Analysis was performed using Kaplan Meier method.
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From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 24.71 months)
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Phase 3: DOR by Derived Investigator Assessment for Arm B Versus Arm C - FAS ORR Subset
Tidsramme: From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 24.71 months)
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DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 by derived investigator assessment, or death due to any cause.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Analysis was performed using Kaplan Meier method.
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From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 24.71 months)
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Phase 3: PFS as Assessed by BICR - FAS
Tidsramme: From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 37.25 months)
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PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by BICR.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
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From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 37.25 months)
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Phase 3: OS - FAS
Tidsramme: From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
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OS was defined as the time from the date of first dose to death due to any cause.
If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact.
Analysis was performed using Kaplan Meier method.
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From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
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Phase 3: PFS by Derived Investigator Assessment - FAS
Tidsramme: From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
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PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause by derived investigator assessment.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
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From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
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Phase 3: TTR as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset
Tidsramme: From date of first dose to CR or PR (maximum up to 24.71 months [107.37 weeks])
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TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by BICR.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
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From date of first dose to CR or PR (maximum up to 24.71 months [107.37 weeks])
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Phase 3: TTR by Derived Investigator Assessment for Arm B vs Arm C - FAS ORR Subset
Tidsramme: From date of first dose to CR or PR (maximum up to 24.71 months [107.37 weeks])
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TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 by derived investigator assessment.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
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From date of first dose to CR or PR (maximum up to 24.71 months [107.37 weeks])
|
|
Phase 3: Progression After Next Line of Treatment (PFS2) - FAS
Tidsramme: From date of randomization to date of discontinuation of next-line treatment after PD or PD2 or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
PFS2 was defined as the time from the date of randomization to the date of discontinuation of next-line treatment after first objective PD by investigator assessment, to second objective disease progression (PD2), or death from any cause, whichever occurred first.
PD2: was progressive disease after the start of subsequent anticancer therapy based on investigator assessment.
PFS2 was censored at start date of next-line anticancer treatment (NTX) if PD date > NTX start date and there was no death, at last contact date if withdrawal of consent date >= date of randomization or end of study or if participant lost to follow-up or if no prior conditions are met or PD and no NTX and there was no death.
|
From date of randomization to date of discontinuation of next-line treatment after PD or PD2 or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: Number of Participants With AEs
Tidsramme: Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event.
AEs included both SAEs and all non-SAEs.
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Through end of the study
|
|
Phase 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
Tidsramme: Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
AEs were graded according to NCI-CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
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Through end of the study
|
|
Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
Tidsramme: Through end of the study
|
The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased.
Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death.
Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
Tidsramme: Through end of the study
|
The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and lipase increased.
Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
Only those chemistry parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: Number of Participants According to Categorization of Vital Signs Data
Tidsramme: Through end of the study
|
The criteria for vital signs included: Systolic blood pressure (mmHg): value <= 90 mmHg and decrease from baseline >= 20 mmHg, and value >= 160 mmHg and increase from baseline >= 20 mmHg.
Diastolic blood pressure (mmHg): value <= 50 mmHg and decrease from baseline >= 15 mmHg, and value >= 100 mmHg and increase from baseline >= 15 mmHg.
Pulse rate (bpm): value <= 50 bpm and decrease from baseline >= 15 bpm, and value >= 120 bpm and increase from baseline >= 15 bpm.
Weight (kg): change >= 20 % decrease from baseline, and change >=10% increase from baseline.
Temperature (degree Celsius): value <=36 degree Celsius, and value >=37.5 degree Celsius.
Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: Number of Participants According to Categorization of ECGs Findings
Tidsramme: Through end of the study
|
ECG criteria included: ECG mean heart rate (bpm): increase from baseline >25% and to a value >100 bpm; decrease from baseline >25% and to a value <50 bpm, PR interval not otherwise specified (msec): new >280 msec, QRS interval not otherwise specified (msec): new >120 msec, QTcF not otherwise specified: new >450 msec; new >480 msec; new >500 msec; increase from baseline >30 msec and increase from baseline >60 msec.
Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients - 30 Item Core Questionnaire (EORTC QLQC30) Global Health Status/Quality of Life Scores (QoL) at Baseline and Week 72
Tidsramme: Baseline and Week 72
|
EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures.
These included five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale.
Global health status/QoL scale ranged from 0 to 100; the higher score represents better level of functioning.
In this outcome measure, global health status/QoL scores are presented.
|
Baseline and Week 72
|
|
Phase 3: EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Visual Analogue Score (VAS) at Baseline and Week 72
Tidsramme: Baseline and Week 72
|
EQ-5D-5L is a standardized measure of health status.
The EQ-5D-5L consisted of EQ-5D-5L descriptive system and the EQ VAS.
For EQ VAS participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
|
Baseline and Week 72
|
|
Phase 3: Number of Participants According to Response to Patient Global Impression of Severity (PGIS) Assessment at Baseline and at Week 30
Tidsramme: Baseline and Week 30
|
PGIS is a single-item scale where participants rated the severity of colorectal cancer as follows: none, mild, moderate, severe and very severe.
|
Baseline and Week 30
|
|
Phase 3: Number of Participants According to Response to Patient Global Impression of Change (PGIC) Assessment at Week 30
Tidsramme: Week 30
|
The PGIC is a single-item scale where participants rated the overall change in colorectal cancer since participant started taking the study medication as follows: much better, a little better, no change, a little worse, and much worse.
|
Week 30
|
|
Phase 3: Trough Plasma Concentration of Encorafenib and Its Metabolite LHY746
Tidsramme: Predose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1
|
Trough plasma concentration of encorafenib and its metabolite LHY746 was measured in this outcome measure.
|
Predose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1
|
|
Phase 3: Cmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
Tidsramme: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
Cmax was observed directly from data.
LHY746 is a metabolite of Encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: AUC6 of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
Tidsramme: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5 and 6 hrs post-dose on Days 1 and 15 of Cycle 1
|
The AUC was estimated from time 0 to 6 hours post dose.
AUC6 was computed using the Linear/Log trapezoidal method.
LHY746 is a metabolite of Encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5 and 6 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: AUCtau of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
Tidsramme: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval.
tau = 24 hrs for QD dosing of encorafenib.
LHY746 is a metabolite of encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: Tmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
Tidsramme: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
Tmax: time (hours) to Cmax.
LHY746 is a metabolite of Encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: CL/F of Encorafenib in Mainland China Participants
Tidsramme: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf).
AUCinf was calculated as AUClast + (Clast*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: Number of Participants Classified According to Microsatellite Instability (MSI) Status as Determined by Retrospective Central Testing of Baseline Tumor Tissue
Tidsramme: Baseline
|
MSI status was classified as follows; microsatellite instability-high (MSI-H): included participants with no negative test results and at least one positive test result, microsatellite stable (MSS): included participants with at least one negative test result and MSI-unknown: included participants with intermediate test results or not analyzed for MSI.
The number of participants as per their MSI status (MSI-H, MSS, and MSI-unknown) have been reported in this outcome measure.
|
Baseline
|
|
Phase 3: Number of Participants According to Circulating Tumor Deoxyribonucleic Acid (ctDNA) Status
Tidsramme: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
ctDNA status was classified as follows; detected: overall variant allele frequency (VAF) was greater than zero, not detected: overall VAF equalled zero, and not evaluable: overall VAF could not be calculated.
The VAF was defined as percentage of deoxyribonucleic acid (DNA) reads at a specific position that show a genetic variant instead of the normal (reference) sequence.
The number of participants as per their ctDNA status (detected, not detected and not evaluable) have been reported in this outcome measure.
|
Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
|
Phase 3: Number of Participants According to B-Raf Serine/Threonine-Protein Kinase (BRAF) Valine 600 (V600) Status From ctDNA
Tidsramme: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
BRAF V600 status from ctDNA was classified as follows; measurable: participants with detectable ctDNA had measurable BRAF V600 tumor biomarker alterations and not measurable: participants with detectable ctDNA did not have measurable BRAF V600 biomarker alterations or overall ctDNA was not detectable.
The number of participants as per their BRAF V600 status from ctDNA (measurable and not measurable) have been reported in this outcome measure.
In this outcome measure, data is presented for participants outside China and Mainland China participants.
|
Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
|
Cohort 3: PFS as Assessed by BICR - FAS
Tidsramme: From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first
|
PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by BICR.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first
|
|
Cohort 3: ORR by Derived Investigator Assessment - FAS
Tidsramme: From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 14.1 months)
|
ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 by derived investigator assessment.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 14.1 months)
|
|
Cohort 3: DOR as Assessed by BICR - FAS
Tidsramme: From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 14.1 months)
|
DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 as assessed by BICR, or death due to any cause.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Analysis was performed using Kaplan Meier method.
|
From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 14.1 months)
|
|
Cohort 3: DOR by Derived Investigator Assessment - FAS
Tidsramme: From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 14.1 months)
|
DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 by derived investigator assessment, or death due to any cause.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Analysis was performed using Kaplan Meier method.
|
From date of first radiographic evidence of response (CR or PR) to earliest documented PD or death due to any cause, whichever occurred first (maximum up to 14.1 months)
|
|
Cohort 3: PFS by Derived Investigator Assessment - FAS
Tidsramme: From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first
|
PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause by derived investigator assessment.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first
|
|
Cohort 3: OS - FAS
Tidsramme: From date of first dose to death due to any cause or censoring date, whichever occurred first
|
OS was defined as the time from the date of first dose to death due to any cause.
If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact.
Analysis was performed using Kaplan Meier method.
|
From date of first dose to death due to any cause or censoring date, whichever occurred first
|
|
Cohort 3: TTR as Assessed by BICR - FAS
Tidsramme: From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by BICR.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
|
From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
|
Cohort 3: TTR by Derived Investigator Assessment - FAS
Tidsramme: From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 by derived investigator assessment.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
|
From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
|
Cohort 3: Number of Participants With AEs
Tidsramme: Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event.
AEs included both SAEs and all non-SAEs.
|
Through end of the study
|
|
Cohort 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
Tidsramme: Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
AEs were graded according to NCI-CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
|
Through end of the study
|
|
Cohort 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
Tidsramme: Through end of the study
|
The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased.
Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death.
Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
Cohort 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
Tidsramme: Through end of the study
|
The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and lipase increased.
Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
Only those chemistry parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
Cohort 3: Number of Participants According to Categorization of Vital Signs Data
Tidsramme: Through end of the study
|
The criteria for vital signs included: Systolic blood pressure (mmHg): value <= 90 mmHg and decrease from baseline >= 20 mmHg, and value >= 160 mmHg and increase from baseline >= 20 mmHg.
Diastolic blood pressure (mmHg): value <= 50 mmHg and decrease from baseline >= 15 mmHg, and value >= 100 mmHg and increase from baseline >= 15 mmHg.
Pulse rate (bpm): value <= 50 bpm and decrease from baseline >= 15 bpm, and value >= 120 bpm and increase from baseline >= 15 bpm.
Weight (kg): change >= 20 % decrease from baseline, and change >=10% increase from baseline.
Temperature (degree Celsius): value <=36 degree Celsius, and value >=37.5 degree Celsius.
Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
|
Through end of the study
|
|
Cohort 3: Number of Participants According to Categorization of ECGs Findings
Tidsramme: Through end of the study
|
ECG criteria included: ECG mean heart rate (bpm): increase from baseline >25% and to a value >100 bpm; decrease from baseline >25% and to a value <50 bpm, PR interval not otherwise specified (msec): new >280 msec, QRS interval not otherwise specified (msec): new >120 msec, QTcF not otherwise specified: new >450 msec; new >480 msec; new >500 msec; increase from baseline >30 msec and increase from baseline >60 msec.
Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
|
Through end of the study
|
|
Cohort 3: EORTC QLQC30 Global Health Status/QoL
Tidsramme: Through end of the study
|
EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures.
These included five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale.
Global health status/QoL scale ranged from 0 to 100; the higher score represents better level of functioning.
|
Through end of the study
|
|
Cohort 3: EQ-5D-5L VAS
Tidsramme: Through end of the study
|
EQ-5D-5L is a standardized measure of health status.
The EQ-5D-5L consisted of EQ-5D-5L descriptive system and the EQ VAS.
For EQ VAS participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
|
Through end of the study
|
|
Cohort 3: Number of Participants According to Response to PGIS Assessment
Tidsramme: Through end of the study
|
PGIS is a single-item scale where participants rated the severity of colorectal cancer as follows: none, mild, moderate, severe and very severe.
|
Through end of the study
|
|
Cohort 3: Number of Participants According to Response to PGIC Assessment
Tidsramme: Through end of the study
|
The PGIC is a single-item scale where participants rated the overall change in colorectal cancer since participant started taking the study medication as follows: much better, a little better, no change, a little worse, and much worse.
|
Through end of the study
|
|
Cohort 3: Trough Plasma Concentration of Encorafenib and Its Metabolite LHY746
Tidsramme: Predose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1
|
Trough plasma concentration of encorafenib and its metabolite LHY746 was measured in this outcome measure.
|
Predose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1
|
|
Cohort 3: Number of Participants Classified According to MSI Status as Determined by Retrospective Central Testing
Tidsramme: Through end of the study
|
MSI status was classified as follows; MSI-H: included participants with no negative test results and at least one positive test result, MSS: included participants with at least one negative test result and MSI-unknown: included participants with intermediate test results or not analyzed for MSI.
The number of participants as per their MSI status (MSI-H, MSS, and MSI-unknown) have been reported in this outcome measure.
|
Through end of the study
|
|
Cohort 3: Number of Participants According to ctDNA Status
Tidsramme: Through end of the study
|
ctDNA status was classified as follows; detected: overall variant allele frequency (VAF) was greater than zero, not detected: overall VAF equalled zero, and not evaluable: overall VAF could not be calculated.
The VAF was defined as percentage of deoxyribonucleic acid (DNA) reads at a specific position that show a genetic variant instead of the normal (reference) sequence.
The number of participants as per their ctDNA status (detected, not detected and not evaluable) have been reported in this outcome measure.
|
Through end of the study
|
|
Cohort 3: Number of Participants According to BRAF V600 Status From ctDNA
Tidsramme: Through end of the study
|
BRAF V600 status from ctDNA was classified as follows; measurable: participants with detectable ctDNA had measurable BRAF V600 tumor biomarker alterations and not measurable: participants with detectable ctDNA did not have measurable BRAF V600 biomarker alterations or overall ctDNA was not detectable.
The number of participants as per their BRAF V600 status from ctDNA (measurable and not measurable) have been reported in this outcome measure.
|
Through end of the study
|
Samarbejdspartnere og efterforskere
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Sponsor
Samarbejdspartnere
Efterforskere
- Studieleder: Pfizer CT.gov Call Center, Pfizer
Publikationer og nyttige links
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Generelle publikationer
- Van Cutsem E, Taieb J, Yaeger R, Yoshino T, Grothey A, Maiello E, Elez E, Dekervel J, Ross P, Ruiz-Casado A, Graham J, Kato T, Ruffinelli JC, Andre T, Carriere Roussel E, Klauck I, Groc M, Vedovato JC, Tabernero J. ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer. J Clin Oncol. 2023 May 10;41(14):2628-2637. doi: 10.1200/JCO.22.01693. Epub 2023 Feb 10.
- Kopetz S, Tabernero J, Elez E. BREAKWATER Phase III: results for encorafenib and cetuximab plus mFOLFOX6 in first-line BRAF V600E-mutant metastatic colorectal cancer. Future Oncol. 2025 Dec;21(28):3585-3588. doi: 10.1080/14796694.2025.2579882. Epub 2025 Nov 13.
- Elez E, Yoshino T, Shen L, Lonardi S, Van Cutsem E, Eng C, Kim TW, Wasan HS, Desai J, Ciardiello F, Yaeger R, Maughan TS, Morris VK, Wu C, Usari T, Laliberte R, Dychter SS, Zhang X, Tabernero J, Kopetz S; BREAKWATER Trial Investigators. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. N Engl J Med. 2025 Jun 26;392(24):2425-2437. doi: 10.1056/NEJMoa2501912. Epub 2025 May 30.
- Kopetz S, Yoshino T, Van Cutsem E, Eng C, Kim TW, Wasan HS, Desai J, Ciardiello F, Yaeger R, Maughan TS, Beyzarov E, Zhang X, Ferrier G, Zhang X, Tabernero J. Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nat Med. 2025 Mar;31(3):901-908. doi: 10.1038/s41591-024-03443-3. Epub 2025 Jan 25.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
21. december 2020
Primær færdiggørelse (Faktiske)
1. marts 2025
Studieafslutning (Anslået)
28. december 2027
Datoer for studieregistrering
Først indsendt
5. oktober 2020
Først indsendt, der opfyldte QC-kriterier
22. oktober 2020
Først opslået (Faktiske)
29. oktober 2020
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
11. juni 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
15. maj 2026
Sidst verificeret
1. maj 2026
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- Kolorektal cancer
- Endetarmskræft
- Gastrointestinale sygdomme
- Sygdomme i fordøjelsessystemet
- Tarmsygdomme
- Kolorektale neoplasmer
- Tyktarmssygdomme
- Tyktarmskræft
- Tarmkræft
- Intestinale neoplasmer
- Gastrointestinal cancer
- Gastrointestinale neoplasmer
- Kræft i fordøjelsessystemet
- Neoplasmer i fordøjelsessystemet
- Endetarmssygdomme
- BRØDVAND Studie
Yderligere relevante MeSH-vilkår
- Neoplasmer efter sted
- Neoplasmer
- Gastrointestinale sygdomme
- Sygdomme i fordøjelsessystemet
- Tyktarmssygdomme
- Rektale neoplasmer
- Kolorektale neoplasmer
- Colon neoplasmer
- Gastrointestinale neoplasmer
- Intestinale neoplasmer
- Tarmsygdomme
- Neoplasmer i fordøjelsessystemet
- Endetarmssygdomme
- Aminosyrer, peptider og proteiner
- Proteiner
- Organiske kemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Nukleinsyrer, nukleotider og nukleosider
- Camptothecin
- Alkaloider
- Enzymer og coenzymer
- Antistoffer, monoklonal, humaniseret
- Antistoffer, monoklonal
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serum globuliner
- Globuliner
- Koordinationskomplekser
- Deoxycytidin
- Cytidin
- Pyrimidin -nukleosider
- Pyrimidiner
- Nukleosider
- Formyltetrahydrofolater
- Tetrahydrofolater
- Folinsyre
- Pterins
- Pteridiner
- Uracil
- Pyrimidinoner
- Coenzymer
- Deoxyribonucleosider
- Capecitabin
- Oxaliplatin
- Bevacizumab
- Irinotecan
- Cetuximab
- Fluorouracil
- Leucovorin
- Levoleucovorin
- Encorafenib
Andre undersøgelses-id-numre
- C4221015
- BREAKWATER (Anden identifikator: Pfizer)
- 2023-509405-77-00 (Registry Identifier: CTIS (EU))
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
JA
IPD-planbeskrivelse
Pfizer vil give adgang til individuelle afidentificerede deltagerdata og relaterede undersøgelsesdokumenter (f.eks.
protokol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) efter anmodning fra kvalificerede forskere og underlagt visse kriterier, betingelser og undtagelser.
Yderligere detaljer om Pfizers datadelingskriterier og proces for at anmode om adgang kan findes på: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .