이전에 치료받지 않은 전이성 대장암 환자를 대상으로 화학 요법을 병용하거나 병용하지 않는 Encorafenib + Cetuximab에 대한 연구
2026년 5월 15일 업데이트: Pfizer
전이성 BRAF V600E-돌연변이 대장암 환자를 대상으로 화학 요법을 포함하거나 포함하지 않는 1차 엔코라페닙과 세툭시맙의 공개 라벨, 멀티센터, 무작위 3상 연구 대 엔코라페닙 및 세툭시맙 플러스 화학 요법의 안전한 도입을 통한 표준 치료 요법
이 연구의 목적은 대장암의 잠재적 치료를 위해 단독으로 또는 표준 화학 요법과 함께 복용하는 두 가지 연구 약물(엔코라페닙 + 세툭시맙)을 평가하는 것입니다.
- 신체의 다른 부분으로 퍼졌습니다(전이성).
- "BRAF"라는 특정 유형의 비정상 유전자가 있습니다. 그리고
- 사전 치료를 받지 않았습니다.
이 연구의 참가자는 다음 연구 치료 중 하나를 받게 됩니다.
- Encorafenib + cetuximab: 이 참가자들은 매일 집에서 encorafenib을 경구 투여받고 연구 클리닉에서 정맥 주사(IV) 주입(정맥 주사)으로 2주에 한 번씩 cetuximab을 투여받습니다.
- Encorafenib + cetuximab + 화학 요법: 이 참가자는 위의 항목에 설명된 방식으로 encorafenib 및 cetuximab을 받게 됩니다. 또한 집에서 IV 주입 및 구강 치료를 통해 표준 화학 요법을 받게 됩니다.
- 단독 화학 요법: 이 참가자는 연구 클리닉에서 IV 주입을 통해 이 조건에 대한 표준 치료인 화학 요법을 받고 집에서 구강 치료를 받습니다.
연구 팀은 최대 약 3년 동안 각 참가자가 연구 치료에 어떻게 반응하는지 모니터링합니다.
연구 개요
상태
모집하지 않고 적극적으로
정황
상세 설명
이 연구의 목적은 encorafenib + cetuximab(EC) 단독 또는 화학 요법과의 병용이 이전에 치료받지 않은 BRAF V600E-돌연변이 mCRC를 가진 참가자에서 현재 표준 치료 화학 요법에 비해 임상 결과를 개선할 수 있는지 여부를 평가하는 것입니다.
encorafenib은 이전에 화학 요법과 병용되지 않았기 때문에 mFOLFOX6와 FOLFIRI와 병용한 EC의 내약성 및 PK는 어떤 화학 요법 조합이 연구의 3상 부분에서 사용됩니다.
연구 유형
중재적
등록 (실제)
841
단계
- 3단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Johannesburg, 남아프리카, 2193
- Wits Health Consortium (Pty) Ltd
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CAPE TOWN
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Rondebosch, CAPE TOWN, 남아프리카, 7700
- Cancercare Rondebosch Oncology
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Eastern Cape
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Port Elizabeth, Eastern Cape, 남아프리카, 6045
- Cancercare Langenhoven Drive Oncology Centre
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Utrecht, 네덜란드, 3584 CX
- Universitair Medisch Centrum Utrecht
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North Brabant
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Eindhoven, North Brabant, 네덜란드, 5623 EJ
- Catharina Ziekenhuis
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North Holland
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Amsterdam, North Holland, 네덜란드, 1066 CX
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
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Oslo, 노르웨이, 0379
- Oslo universitetssykehus, Radiumhospitalet
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Oslo, 노르웨이, 0450
- Oslo Universitetssykehus Ullevål
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Sør-trøndelag
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Trondheim, Sør-trøndelag, 노르웨이, 7030
- St. Olavs Hospital
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Vest-agder
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Kristiansand, Vest-agder, 노르웨이, N-4615
- Sørlandet Sykehus Kristiansand
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Auckland, 뉴질랜드, 1023
- Auckland City Hospital
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Kaohsiung City, 대만, 807
- Kaohsiung Medical University Chung-Ho Memorial Hospital
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Taichung, 대만, 404
- China Medical University Hospital
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Tainan, 대만, 704
- National Cheng-Kung University Hospital
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Tainan, 대만, 73657
- Chi Mei Hospital, Liouying
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Taipei, 대만, 100
- National Taiwan University Hospital
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Taipei, 대만, 11031
- Taipei Medical University Hospital
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Taipei, 대만, 112
- Taipei Veterans General Hospital
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Taoyuan, 대만, 333
- Chang Gung Medical Foundation-Linkou Branch
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Busan, 대한민국, 49201
- Dong-A University Hospital
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Daegu, 대한민국, 41404
- Kyungpook National University Chilgok Hospital
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Incheon, 대한민국, 21565
- Gachon University Gil Medical Center
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Seoul, 대한민국, 03080
- Seoul National University Hospital
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Seoul, 대한민국, 05505
- Asan Medical Center
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Seoul, 대한민국, 06351
- Samsung Medical Center
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Seoul, 대한민국, 03722
- Severance Hospital, Yonsei University Health System
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Seoul, 대한민국, 02841
- Korea University Anam Hospital
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Gyeonggi-do
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Goyang-si, Gyeonggi-do, 대한민국, 10408
- National Cancer Center
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Copenhagen, 덴마크, 2100
- Rigshospitalet
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Herlev, 덴마크, 2730
- Herlev and Gentofte Hospital
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Odense C, 덴마크, 5000
- Odense University Hospital
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North Denmark
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Aalborg, North Denmark, 덴마크, 9000
- Aalborg Universitetshospital, Syd
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Region Syddanmark
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Vejle, Region Syddanmark, 덴마크, 7100
- Vejle Sygehus
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Vejle, Region Syddanmark, 덴마크, 7100
- Vejle Hospital-Sygehus Lillebaelt
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Berlin, 독일, 10707
- Onkologische Schwerpunktpraxis Kurfuerstendamm
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Berlin, 독일, 13125
- HELIOS Klinikum Berlin Buch GmbH
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Charlottenburg, 독일, 10719
- Radiologie Berlin
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Dresden, 독일, 01307
- Universitätsklinikum Carl Gustav Carus Dresden
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Dresden, 독일, 01307
- Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus
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Hamburg, 독일, 20249
- Facharztzentrum Eppendorf
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Hamburg, 독일, 22045
- ZytoService Deutschland GmbH, Standort-Hamburg-Jenfeld
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Hamburg, 독일, 22297
- Radiologie im Israelitischen Krankenhaus
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Bavaria
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Munich, Bavaria, 독일, 81737
- Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
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Hesse
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Frankfurt am Main, Hesse, 독일, 60488
- Institut für Klinisch Onkologische Forschung
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Lower Saxony
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Hanover, Lower Saxony, 독일, 30625
- Medizinische Hochschule Hannover
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Saxony
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Leipzig, Saxony, 독일, 04103
- Universitatsklinikum Leipzig
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Chelyabinsk, 러시아 제국, 454087
- GBUZ
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Kaluga, 러시아 제국, 248007
- Kaluga Regional Clinical Oncology Center
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Moscow, 러시아 제국, 119991
- FSAEI HE I.M Sechenov First MSMU MoH Russia (Sechenovskiy University),
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Omsk, 러시아 제국, 644013
- BHI of Omsk region "Clinical Oncology Dispensary"
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Omsk, 러시아 제국, 644046
- BHI of Omsk region "Clinical Oncology Dispensary"
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Saint Petersburg, 러시아 제국, 191025
- LLC "Medicina Severnoy Stolitsy"
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Saint Petersburg, 러시아 제국, 192007
- LLC "Severo-Zapadny Medical Center"
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Saint Petersburg, 러시아 제국, 195271
- Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg
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Saint Petersburg, 러시아 제국, 197022
- LLC "Eurocityclinic"
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Saint Petersburg, 러시아 제국, 197758
- FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov
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Yaroslavl, 러시아 제국, 150054
- SHI YR Regional Clinical Oncology Hospital
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Sankt-Peterburg
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Pushkin, Sankt-Peterburg, 러시아 제국, 196603
- Private Medical Institution "Euromedservice"
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Oaxaca City, 멕시코, 68020
- Centro de Investigacion Clinica de Oaxaca
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Nuevo León
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Monterrey, Nuevo León, 멕시코, 64000
- Accelerium, S. de R.L. de C.V.
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Arizona
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Phoenix, Arizona, 미국, 85054
- Mayo Clinic Hospital
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Scottsdale, Arizona, 미국, 85259
- Mayo Clinic in Arizona - Scottsdale
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California
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Los Angeles, California, 미국, 90033
- USC / Norris Comprehensive Cancer Center
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Los Angeles, California, 미국, 90033
- USC/Norris Comprehensive Cancer Center
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Los Angeles, California, 미국, 90033
- Keck Hospital of USC
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Los Angeles, California, 미국, 90033
- LAC & USC Medical Center
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Los Angeles, California, 미국, 90033
- USC/Norris Comprehensive Cancer Center/Investigational Drug Services
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Pasadena, California, 미국, 91105
- Keck Hospital of USC Pasadena
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Florida
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Aventura, Florida, 미국, 33180
- Mount Sinai Comprehensive Cancer Center, Aventura
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Miami Beach, Florida, 미국, 33140
- Mount Sinai Medical Center
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Miami Beach, Florida, 미국, 33140
- Mount Sinai Comprehensive Cancer Center
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Plantation, Florida, 미국, 33322
- BRCR Medical Center Inc.
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Plantation, Florida, 미국, 33322
- BRCR Global
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Illinois
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Chicago, Illinois, 미국, 60637
- University Of Chicago Medical Center
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Chicago, Illinois, 미국, 60611
- UChicago Medicine - River East
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Flossmoor, Illinois, 미국, 60422
- UChicago Medicine at Ingalls - Flossmoor
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Harvey, Illinois, 미국, 60426
- UChicago Medicine Ingalls Memorial
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New Lenox, Illinois, 미국, 60451
- University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
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Orland Park, Illinois, 미국, 60462
- The University of Chicago Medicine Center for Advanced Care Orland Park
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Tinley Park, Illinois, 미국, 60477
- UChicago Medicine at Ingalls - Tinley Park
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Louisiana
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New Orleans, Louisiana, 미국, 70121
- Ochsner Clinic Foundation
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Minnesota
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Rochester, Minnesota, 미국, 55905
- Mayo Clinic Rochester
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Missouri
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City of Saint Peters, Missouri, 미국, 63376
- Siteman Cancer Center - St Peters
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Creve Coeur, Missouri, 미국, 63141
- Siteman Cancer Center - West County
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Florissant, Missouri, 미국, 63031
- Siteman Cancer Center - North County
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St Louis, Missouri, 미국, 63110
- Washington University School of Medicine
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St Louis, Missouri, 미국, 63129
- Siteman Cancer Center - South County
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St Louis, Missouri, 미국, 63110
- Barnes- Jewish Hospital
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Nebraska
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Omaha, Nebraska, 미국, 68130
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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Omaha, Nebraska, 미국, 68124
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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Omaha, Nebraska, 미국, 68114
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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Papillion, Nebraska, 미국, 68046
- Oncology Hematology West PC dba Nebraska Cancer Specialists
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New Jersey
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Basking Ridge, New Jersey, 미국, 07920
- Memorial Sloan Kettering Cancer Center - Basking Ridge
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Berkeley Heights, New Jersey, 미국, 07922
- Summit Medical Group
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Florham Park, New Jersey, 미국, 07932
- Summit Medical Group
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Middletown, New Jersey, 미국, 07748
- Memorial Sloan Kettering Cancer Center- Monmouth
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Montvale, New Jersey, 미국, 07645
- Memorial Sloan Kettering Cancer Center- Bergen
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New York
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Commack, New York, 미국, 11725
- Memorial Sloan Kettering Cancer Center Commack
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Harrison, New York, 미국, 10604
- Memorial Sloan Kettering Cancer Center - Westchester
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New York, New York, 미국, 10022
- Memorial Sloan Kettering Cancer Center
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New York, New York, 미국, 10065
- Memorial Sloan Kettering Cancer Center - Main Campus
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Uniondale, New York, 미국, 11553
- Memorial Sloan Kettering Cancer Center- Nassau
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Ohio
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Cleveland, Ohio, 미국, 44195
- Cleveland Clinic
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Cleveland, Ohio, 미국, 44195
- Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
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Columbus, Ohio, 미국, 43221
- Martha Morehouse Medical plaza
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Columbus, Ohio, 미국, 43210
- The Ohio State University James Cancer Hospital and Solove Research Institute
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Columbus, Ohio, 미국, 43212
- Stefanie Spielman Comprehensive Breast Cancer
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Columbus, Ohio, 미국, 43210
- The Ohio State University Wexner Medical Center Investigational Drug Services
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Oklahoma
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Oklahoma City, Oklahoma, 미국, 73104
- University of Oklahoma Health Sciences Center, OU Health Stephenson Cancer Center
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Oregon
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Portland, Oregon, 미국, 97213
- Providence Cancer Institute Franz Clinic
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Portland, Oregon, 미국, 97213
- Providence Portland Medical Center
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Portland, Oregon, 미국, 97225
- Providence St Vincent Medical Center
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Portland, Oregon, 미국, 97225
- Providence Onc and Heme Care Clinic - Westside
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Pennsylvania
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Pittsburgh, Pennsylvania, 미국, 15232
- UPMC Hillman Cancer Center
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Tennessee
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Germantown, Tennessee, 미국, 38138
- The West Clinic. PLLC. dba West Cancer Center
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Nashville, Tennessee, 미국, 37232
- Vanderbilt-Ingram Cancer Center
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Nashville, Tennessee, 미국, 37232
- Henry-Joyce Cancer Clinic
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Texas
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Houston, Texas, 미국, 77030
- The University of Texas MD Anderson Cancer Center
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Virginia
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Richmond, Virginia, 미국, 23219
- Virginia Commonwealth University
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Washington
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Seattle, Washington, 미국, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, 미국, 98195
- University of Washington Medical Center
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Wisconsin
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Madison, Wisconsin, 미국, 53792
- University of Wisconsin Clinical Science Center
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Antwerp, 벨기에, 2020
- ZNA Middelheim
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Leuven, 벨기에, 3000
- UZ Leuven
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Liège, 벨기에, 4000
- Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
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Wilrijk, 벨기에, 2610
- ZAS Augustinus
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Bruxelles-capitale, Région de
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Brussels, Bruxelles-capitale, Région de, 벨기에, 1070
- Université Libre de Bruxelles - Hôpital Erasme
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Brussels, Bruxelles-capitale, Région de, 벨기에, 1200
- Cliniques universitaires Saint-Luc
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Hainaut
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Charleroi, Hainaut, 벨기에, 6060
- Grand Hôpital de Charleroi
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West-vlaanderen
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Kortrijk, West-vlaanderen, 벨기에, 8500
- AZ Groeninge Campus Kennedylaan
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Gabrovo, 불가리아, 5300
- MHAT "Dr. Tota Venkova" AD
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Plovdiv, 불가리아, 4000
- MHAT Central Onco Hospital OOD
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Plovdiv, 불가리아, 4004
- Complex Oncology Center - Plovdiv EOOD
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Sofia, 불가리아, 1303
- Medical Center Nadezhda Clinical EOOD
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Sofia, 불가리아, 1407
- Acibadem City Clinic MHAT Tokuda
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Sofia, 불가리아, 1750
- University Multiprofile Hospital for Active Treatment Sofiamed
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Pazardzhik
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Panagyurishte, Pazardzhik, 불가리아, 4500
- MHAT Uni Hospital OOD
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, 브라질, 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, 브라질, 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, 브라질, 89010-340
- Reichow - Centro de Ensino e Pesquisa
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Itajaí, Santa Catarina, 브라질, 88301-220
- Clinica de Neoplasias Litoral
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São Paulo
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Barretos, São Paulo, 브라질, 14784400
- Fundacao Pio XII - Hospital de Cancer de Barretos
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Barretos, São Paulo, 브라질, 14.780-070
- Fundacao Pio XII - Hospital de Cancer de Barretos
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Santo André, São Paulo, 브라질, 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, 브라질, 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, 브라질, 15090000
- Fundação Faculdade Regional de Medicina de São José do Rio Preto
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Stockholm, 스웨덴, 171 76
- Department of Pelvic cancer, colorecta section, Karolinska University Hospital
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Stockholms LÄN [se-01]
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Solna, Stockholms LÄN [se-01], 스웨덴, 171 64
- Karolinska Universitetssjukhuset Solna
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Uppsala LÄN [se-03]
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Uppsala, Uppsala LÄN [se-03], 스웨덴, 751 85
- Akademiska Sjukhuset
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Västerbottens LÄN [se-24]
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Umeå, Västerbottens LÄN [se-24], 스웨덴, 90185
- Norrlands universitetssjukhus
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Västra Götalands LÄN [se14]
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Gothenburg, Västra Götalands LÄN [se14], 스웨덴, 413 45
- Sahlgrenska Universitetssjukhuset
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Barcelona, 스페인, 08035
- Hospital Universitario Vall d'Hebron
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Barcelona, 스페인, 08036
- Hospital Clinic Barcelona
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Madrid, 스페인, 28034
- Hospital Universitario Ramon y Cajal
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Madrid, 스페인, 28041
- Hospital Universitario 12 de Octubre
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Madrid, 스페인, 28007
- Hospital General Universitario Gregorio Marañón
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Seville, 스페인, 41013
- Hospital Universitario Virgen del Rocío
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Valencia, 스페인, 46010
- Hospital Clínico Universitario de Valencia
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Valencia, 스페인, 46014
- Hospital General Universitario de Valencia
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Zaragoza, 스페인, 50009
- Hospital Universitario Miguel Servet
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A Coruña
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Santiago de Compostela, A Coruña, 스페인, 15706
- Complejo Hospitalario Universitario Santiago de Compostela
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Alicante
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Elche, Alicante, 스페인, 03203
- Hospital General Universitario de Elche
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Barcelona
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L'Hospitalet de Llobregat, Barcelona, 스페인, 08908
- ICO L'Hospitalet (Hospital Duran i Reynals)
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-
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Bratislava, 슬로바키아, 833 10
- Narodny onkologicky ustav
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Košice, 슬로바키아, 04191
- Vychodoslovensky onkologicky ustav, a.s.
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-
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-
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Buenos Aires, 아르헨티나, 1426
- Instituto Medico Especializado Alexander Fleming
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Córdoba, 아르헨티나, X5004FHP
- Clínica Universitaria Reina Fabiola
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Córdoba, 아르헨티나, X5016KEH
- Hospital Privado Centro Medico de Cordoba
-
-
Tucumán Province
-
San Miguel de Tucumán, Tucumán Province, 아르헨티나, 4000
- Centro Medico San Roque
-
-
-
-
-
Birmingham, 영국, B9 5SS
- Heartlands Hospital
-
London, 영국, W12 0HS
- Hammersmith Hospital, Imperial College Healthcare NHS Trust
-
London, 영국, W6 8RF
- Hammersmith Hospital
-
Oxford, 영국, OX3 7LE
- Churchill Hospital - Oncology
-
-
HIGH Heaton
-
Newcastle upon Tyne, HIGH Heaton, 영국, NE7 7DN
- Freeman Hospital
-
-
Surrey
-
Sutton, Surrey, 영국, SM2 5PT
- Royal Marsden NHS Foundation Trust
-
-
-
-
-
Dnipro, 우크라이나, 49102
- Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
-
Ivano-Frankivsk, 우크라이나, 76018
- Ivano-Frankivsk National Medical University
-
Ivano-Frankivsk, 우크라이나, 76018
- MNPE "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Regional Council"
-
Kryvyi Rih, 우크라이나, 50048
- Communal enterprise "Kryvyi Rih Oncology Dispensary" of Dnipropetrovsk Regional Council
-
-
-
-
-
Brescia, 이탈리아, 25124
- Fondazione Poliambulanza Istituto Ospedaliero
-
Milan, 이탈리아, 20141
- Istituto Europeo di Oncologia IRCCS
-
Naples, 이탈리아, 80131
- Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" di Napoli
-
Padova, 이탈리아, 35128
- IRCCS Istituto Oncologico Veneto (IOV)
-
Reggio Emilia, 이탈리아, 42123
- Azienda USL - IRCCS di Reggio Emilia - Arcispedale Santa Maria Nuova
-
-
Cagliari
-
Monserrato (CA), Cagliari, 이탈리아, 09042
- Azienda Ospedaliera Universitaria di Cagliari - Presidio Policlinico Universitario "D.Casula"
-
-
Foggia
-
San Giovanni Rotondo, Foggia, 이탈리아, 71013
- IRCCS Casa Sollievo della Sofferenza
-
-
Milano
-
Milan, Milano, 이탈리아, 20162
- ASST Grande Ospedale Metropolitano Niguarda
-
-
Torino
-
Candiolo, Torino, 이탈리아, 10060
- Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo IRCCS
-
Orbassano, Torino, 이탈리아, 10043
- Azienda Ospedaliero Universitaria San Luigi Gonzaga
-
-
-
-
Maharashtra
-
Mumbai, Maharashtra, 인도, 400012
- Tata Memorial Hospital
-
Pune, Maharashtra, 인도, 411 004
- Deenanath Mangeshkar Hospital & Research Centre
-
Pune, Maharashtra, 인도, 411 004
- Sahyadri Speciality Hospital
-
Thane, Maharashtra, 인도, 401107
- Bhakti Vedanta Hospital and Research Institute
-
-
National Capital Territory of Delhi
-
New Delhi, National Capital Territory of Delhi, 인도, 110085
- Rajiv Gandhi Cancer Institute And Research Centre
-
-
Rajasthan
-
Jaipur, Rajasthan, 인도, 302004
- Sawai Man Singh Medical College Hospital (SMS Hospital)
-
-
-
-
-
Fukuoka, 일본, 811-1395
- National Hospital Organization Kyushu Cancer Center
-
Osaka, 일본, 540-0006
- National Hospital Organization - Osaka National Hospital - Institute For Clinical Research
-
-
Chiba
-
Chiba, Chiba, 일본, 260-8717
- Chiba Cancer Center
-
Kashiwa, Chiba, 일본, 277-8577
- National Cancer Center Hospital East
-
-
Hokkaido
-
Sapporo, Hokkaido, 일본, 060-8648
- Hokkaido University Hospital
-
-
Ishikawa-ken
-
Kanazawa, Ishikawa-ken, 일본, 920-8641
- Kanazawa University Hospital
-
-
Kanagawa
-
Kawasaki, Kanagawa, 일본, 216-8511
- St. Marianna University Hospital
-
Yokohama, Kanagawa, 일본, 2418515
- Kanagawa Cancer Center
-
-
Nagoya, Aichi
-
Nagoya, Nagoya, Aichi, 일본, 464-8681
- Aichi Cancer Center Hospital
-
-
Osaka
-
Osaka, Osaka, 일본, 5418567
- Osaka Prefectural Hospital Organization Osaka International Cancer Institute
-
Sayama, Osaka, 일본, 589-8511
- Kindai University Hospital
-
Suita, Osaka, 일본, 565-0871
- Osaka University Hospital
-
Takatsuki, Osaka, 일본, 569-8686
- Osaka Medical and Pharmaceutical University Hospital
-
-
Saitama
-
Hidaka, Saitama, 일본, 350-1298
- Saitama Medical University International Medical Center
-
Ina-machi, Saitama, 일본, 362-0806
- Saitama Prefectural Cancer Center
-
-
Shizuoka
-
Nakatogari, Shizuoka, 일본, 411-8777
- Shizuoka Cancer Center
-
-
Tokyo
-
Chuo-ku, Tokyo, 일본, 104-0045
- National Cancer Center Hospital
-
Koto-ku, Tokyo, 일본, 135-8550
- The Cancer Institute Hospital of JFCR
-
Shinjuku-ku, Tokyo, 일본, 160-8582
- Keio University Hospital
-
-
-
-
-
Shanghai, 중국, 201321
- Fudan University Shanghai Cancer Center
-
Tianjin, 중국, 300000
- Tianjin Union Medical Center
-
-
Beijing Municipality
-
Beijing, Beijing Municipality, 중국, 100142
- Beijing Cancer Hospital
-
Beijing, Beijing Municipality, 중국, 100034
- Peking University First Hospital
-
Beijing, Beijing Municipality, 중국, 100730
- Beijing Hospital
-
Beijing, Beijing Municipality, 중국, 100021
- Cancer Hospital Chinese Academy of Medical Science
-
-
Chongqing Municipality
-
Chongqing, Chongqing Municipality, 중국, 400030
- Chongqing University Cancer Hospital
-
-
Fujian
-
Fuzhou, Fujian, 중국, 350001
- Fujian Medical University Union Hospital
-
-
Guangdong
-
Guangzhou, Guangdong, 중국, 510655
- The Sixth Affiliated Hospital of Sun Yat-sen University
-
-
Guangxi
-
Nanning, Guangxi, 중국, 530200
- Affiliated Tumor Hospital of Guangxi Medical University
-
-
Hubei
-
Wuhan, Hubei, 중국, 430030
- Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
-
-
Hunan
-
Changsha, Hunan, 중국, 410013
- The Third XIANGYA Hospital of Central South University
-
Changsha, Hunan, 중국, 410011
- The Second Xiangya Hospital of Central South University
-
-
Jiangsu
-
Nanjing, Jiangsu, 중국, 210008
- Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
-
-
Liaoning
-
Shenyang, Liaoning, 중국, 110022
- Shengjing Hospital of China Medical University
-
-
Shandong
-
Jinan, Shandong, 중국, 250117
- Shandong province cancer hospital
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, 중국, 200080
- Shanghai General Hospital
-
Shanghai, Shanghai Municipality, 중국, 201800
- Ruijin Hospital Shanghai Jiaotong University School of Medicine
-
-
Sichuan
-
Chengdu, Sichuan, 중국, 610041
- Sichuan province cancer hospital
-
-
Yunnan
-
Kunming, Yunnan, 중국, 650118
- Yunnan Cancer Hospital(The Third Affiliated Hospital of Kunming Medical University)
-
-
Zhejiang
-
Hangzhou, Zhejiang, 중국, 310000
- The second Affiliated Hospital of College of Medicine, Zhejiang University
-
-
-
-
-
Olomouc, 체코, 779 00
- Fakultni Nemocnice Olomouc
-
Prague, 체코, 180 81
- Fakultní nemocnice Bulovka
-
-
Brno-město
-
Brno, Brno-město, 체코, 625 00
- Fakultní nemocnice Brno Bohunice
-
-
Hradec Králové
-
Hradec Králové, Hradec Králové, 체코, 500 05
- Fakultni nemocnice Hradec Kralove
-
-
Praha 4
-
Prague, Praha 4, 체코, 14059
- Fakultni Thomayerova nemocnice
-
-
-
-
Alberta
-
Calgary, Alberta, 캐나다, T2N 4N2
- Alberta Health Services - Cancer Care, Tom Baker Cancer Centre
-
Calgary, Alberta, 캐나다, T3N 4N1
- Arthur J.E. Child Comprehensive Cancer Centre
-
Edmonton, Alberta, 캐나다, T6G 1Z2
- Cross Cancer Institute
-
Edmonton, Alberta, 캐나다, T6G 2C8
- Alberta Health Services and The Governors of The University of Alberta
-
-
Ontario
-
London, Ontario, 캐나다, N6A 5W9
- London Regional Cancer Program, London Health Sciences Centre
-
Toronto, Ontario, 캐나다, M4N 3M5
- Sunnybrook Health Sciences Centre
-
-
Quebec
-
Montreal, Quebec, 캐나다, H3T 1E2
- Jewish General Hospital
-
-
-
-
-
Brzozów, 폴란드, 36-200
- Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
-
Bytom, 폴란드, 41-902
- Wojewodzki Szpital Specjalistyczny Nr 4 w Bytomiu Oddzial Onkologii
-
Gdansk, 폴란드, 80-219
- Copernicus Podmiot Leczniczy Sp. z o.o. Wojewódzkie Centrum Onkologii
-
Gdansk, 폴란드, 80-219
- COPERNICUS PL sp. z. o. o. Wojewodzkie Centrum Onkologii w Gdansku Ambulatoryjna
-
-
Greater Poland Voivodeship
-
Konin, Greater Poland Voivodeship, 폴란드, 62-500
- Przychodnia Lekarska KOMED
-
-
-
-
-
Oulu, 핀란드, 90220
- Oulu University Hospital
-
Pori, 핀란드, 28500
- Satakunnan Keskussairaala
-
Tampere, 핀란드, 33521
- Tampereen yliopistollinen sairaala
-
Tampere, 핀란드, 33520
- Tampereen yliopistollinen sairaala
-
Turku, 핀란드, 20520
- Turku University Hospital
-
-
Southwest Finland
-
Turku, Southwest Finland, 핀란드, 20520
- Turku University Hospital
-
-
Uusimaa
-
Helsinki, Uusimaa, 핀란드, 00290
- Helsinki University Central Hospital
-
Helsinki, Uusimaa, 핀란드, 00180
- Docrates Syöpäsairaala
-
-
-
-
New South Wales
-
Camperdown, New South Wales, 호주, 2050
- Chris O'Brien Lifehouse
-
Liverpool, New South Wales, 호주, 2170
- Liverpool Hospital
-
St Leonards, New South Wales, 호주, 2065
- GenesisCare North Shore
-
St Leonards, New South Wales, 호주, 2065
- GenesisCare - North Shore
-
-
Queensland
-
Herston, Queensland, 호주, 4029
- Royal Brisbane and Women's Hospital
-
Woolloongabba, Queensland, 호주, 4102
- Princess Alexandra Hospital
-
-
South Australia
-
Adelaide, South Australia, 호주, 5011
- The Queen Elizabeth Hospital
-
Adelaide, South Australia, 호주, 5000
- Central Adelaide Local Health Network Incorporated
-
-
Victoria
-
Clayton, Victoria, 호주, 3168
- Monash Health
-
Heidelberg, Victoria, 호주, 3084
- Austin Health
-
Melbourne, Victoria, 호주, 3000
- Peter MacCallum Cancer Centre
-
Melbourne, Victoria, 호주, 3004
- Alfred Health
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
16년 이상 (어린이, 성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
설명
포함 기준:
- Safety Lead-In = 남성/여성 ≥ 18세
- 3단계: 16세 이상의 남성/여성(현지에서 허용되는 경우)
- BRAF V600E 돌연변이를 포함하는 조직학적 또는 세포학적으로 확인된 IV기 CRC
- 전이성 환경에서 사전 전신 치료
- SLI: 0-1 요법
- 3단계: 없음
- 재발/전이가 adj/neoadjuvant 치료 종료 후 < 6개월인 경우 전이성 치료로 간주되는 이전 보조 또는 신보강 요법
- Measurable disease (Phase 3) / Measurable or evaluable disease (Safety Lead-in)
- ECOG PS 0-1
- 적절한 장기 기능
제외 기준:
- 참가자가 기존 의학적 상태로 인해 면역 체크포인트 억제제를 받을 자격이 없는 경우를 제외하고 국소적으로 확인되었거나 알려지지 않은 MSI-H 또는 dMMR 종양
- 투여 시작 전 2주 동안 활동성 세균 또는 바이러스 감염
- 증상이 있는 뇌 전이
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 안전 리드인 코호트 1
Encorafenib 300 mg 1일 1회 경구 Cetuximab 500 mg/m2(120분 IV 주입) 격주마다 Irinotecan 180 mg/m2(90분 IV 주입) 격주 Leucovorin 400 mg/m2(120분 IV 주입) 격주 주 5-FU 400mg/m2 IV 볼루스, 이후 5-FU 2400mg/m2 연속 IV 주입
|
75mg 캡슐
다른 이름들:
정맥 주사 100 mg/바이알, 200 mg/바이알 또는 500 mg/바이알
다른 이름들:
정맥주입액 40 mg/바이알, 100 mg/바이알 또는 300 mg/바이알
다른 이름들:
주사 50mg/바이알, 100mg/바이알, 200mg/바이알 또는 350mg/바이알
다른 이름들:
정맥 주사 250 mg/바이알, 500 mg/바이알 또는 1000 mg/바이알
다른 이름들:
|
|
실험적: 안전 리드인 코호트 2
Encorafenib 300 mg 1일 1회 경구 Cetuximab 500 mg/m2(120분 IV 주입) 2주마다 Oxaliplatin 85 mg/m2(120분 IV 주입) 2주마다 Leucovorin 400 mg/m2(120분 IV 주입) 2주마다 5-FU 400mg/m2 IV 볼루스, 이후 5-FU 2400mg/m2 연속 IV 주입, 46-48시간 동안 2주마다
|
75mg 캡슐
다른 이름들:
정맥 주사 100 mg/바이알, 200 mg/바이알 또는 500 mg/바이알
다른 이름들:
주사 50mg/바이알, 100mg/바이알, 200mg/바이알 또는 350mg/바이알
다른 이름들:
정맥 주사 250 mg/바이알, 500 mg/바이알 또는 1000 mg/바이알
다른 이름들:
정맥주사액용 분말 50 mg/vial, 100 mg/vial 또는 200 mg/vial
다른 이름들:
|
|
실험적: 3단계 암 A
Encorafenib 300mg 경구 1일 1회 Cetuximab 500mg/m2(120분 IV 주입) 2주마다
|
75mg 캡슐
다른 이름들:
정맥 주사 100 mg/바이알, 200 mg/바이알 또는 500 mg/바이알
다른 이름들:
|
|
실험적: 3단계 팔 B
Encorafenib 300 mg 1일 1회 경구 Cetuximab 500 mg/m2(120분 IV 주입) 2주마다 Oxaliplatin 85 mg/m2(120분 IV 주입) 2주마다 Leucovorin 400 mg/m2(120분 IV 주입) 2주마다 5-FU 400mg/m2 IV 볼루스, 이후 5-FU 2400mg/m2 연속 IV 주입, 46-48시간 동안 2주마다
|
75mg 캡슐
다른 이름들:
정맥 주사 100 mg/바이알, 200 mg/바이알 또는 500 mg/바이알
다른 이름들:
주사 50mg/바이알, 100mg/바이알, 200mg/바이알 또는 350mg/바이알
다른 이름들:
정맥 주사 250 mg/바이알, 500 mg/바이알 또는 1000 mg/바이알
다른 이름들:
정맥주사액용 분말 50 mg/vial, 100 mg/vial 또는 200 mg/vial
다른 이름들:
|
|
활성 비교기: 3단계 암 C
2주마다: Oxaliplatin 85mg/m2(120분 IV 주입) Leucovorin 400mg/m2(120분 IV 주입) 5-FU 400mg/m2 볼루스, 이후 5-FU 2400mg/m2 연속 IV 주입 46~48시간 베바시주맙(선택 사항, 처방 지침에 따라 제공) -또는- 2주마다: 이리노테칸 165mg/m2(90분 IV 주입) 옥살리플라틴 85mg/m2(120분 IV 주입) 류코보린 400mg/m2( 120분 IV 주입) 46 48시간 동안 5-FU 2400 또는 3200 mg/m2 연속 IV 주입 베바시주맙 1일 2회 1000 mg/m2 경구 정제(선택 사항, 처방 지침에 따라 제공)
|
정맥주입액 40 mg/바이알, 100 mg/바이알 또는 300 mg/바이알
다른 이름들:
주사 50mg/바이알, 100mg/바이알, 200mg/바이알 또는 350mg/바이알
다른 이름들:
정맥 주사 250 mg/바이알, 500 mg/바이알 또는 1000 mg/바이알
다른 이름들:
정맥주사액용 분말 50 mg/vial, 100 mg/vial 또는 200 mg/vial
다른 이름들:
150mg 또는 500mg 태블릿
다른 이름들:
정맥내 사용을 위한 선택적 주사 100 mg/vial 또는 400 mg/vial
다른 이름들:
|
|
실험적: 코호트 3군 D
Encorafenib 300 mg 1일 1회 경구 Cetuximab 500 mg/m2(120분 IV 주입) 격주마다 Irinotecan 180 mg/m2(90분 IV 주입) 격주 Leucovorin 400 mg/m2(120분 IV 주입) 격주 주 5-FU 400mg/m2 IV 볼루스, 이후 5-FU 2400mg/m2 연속 IV 주입
|
75mg 캡슐
다른 이름들:
정맥 주사 100 mg/바이알, 200 mg/바이알 또는 500 mg/바이알
다른 이름들:
정맥주입액 40 mg/바이알, 100 mg/바이알 또는 300 mg/바이알
다른 이름들:
주사 50mg/바이알, 100mg/바이알, 200mg/바이알 또는 350mg/바이알
다른 이름들:
정맥 주사 250 mg/바이알, 500 mg/바이알 또는 1000 mg/바이알
다른 이름들:
|
|
활성 비교기: 코호트 3군 E
2주마다 Irinotecan 180 mg/m2(90분 IV 주입), 2주마다 Leucovorin 400 mg/m2(120분 IV 주입), 5-FU 400 mg/m2 IV 볼루스, 그 다음 5-FU 2400 mg/m2 2주마다 46~48시간 동안 지속적으로 IV 주입, Bevacizumab(선택 사항, 처방 지침에 따라 제공됨)
|
정맥주입액 40 mg/바이알, 100 mg/바이알 또는 300 mg/바이알
다른 이름들:
주사 50mg/바이알, 100mg/바이알, 200mg/바이알 또는 350mg/바이알
다른 이름들:
정맥 주사 250 mg/바이알, 500 mg/바이알 또는 1000 mg/바이알
다른 이름들:
정맥내 사용을 위한 선택적 주사 100 mg/vial 또는 400 mg/vial
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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SLI: Number of Participants With Dose Limiting Toxicity (DLTs)
기간: Cycle 1 (28 days)
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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.
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Cycle 1 (28 days)
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Phase 3: Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) for Arm B vs Arm C - FAS
기간: 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)
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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.
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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)
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Phase 3: Objective Response Rate (ORR) as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset
기간: 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)
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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.
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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)
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Cohort 3: ORR as Assessed by BICR for Arm D vs Arm E - FAS
기간: 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)
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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 14.1 months)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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SLI: Number of Participants With Adverse Events (AEs)
기간: 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/ 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.
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Through end of the study
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SLI: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
기간: 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.
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.
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Through end of the study
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SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
기간: Through end of the study
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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.
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Through end of the study
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SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
기간: Through end of the study
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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.
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Through end of the study
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SLI: Number of Participants According to Categorization of Vital Signs Data
기간: Through end of the study
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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.
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Through end of the study
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SLI: Number of Participants According to Categorization of Electrocardiogram (ECGs) Findings
기간: Through end of the study
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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.
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Through end of the study
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SLI: Number of Participants With Dose Modification of Any Study Intervention Due to AEs
기간: 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.
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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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])
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Phase 3: Progression After Next Line of Treatment (PFS2) - FAS
기간: 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)
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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.
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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)
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Phase 3: Number of Participants With AEs
기간: 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/ 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
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Phase 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
기간: 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/ 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
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Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
기간: Through end of the study
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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.
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Through end of the study
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Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
기간: Through end of the study
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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.
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Through end of the study
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Phase 3: Number of Participants According to Categorization of Vital Signs Data
기간: Through end of the study
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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.
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Through end of the study
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Phase 3: Number of Participants According to Categorization of ECGs Findings
기간: Through end of the study
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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.
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Through end of the study
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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
기간: Baseline and Week 72
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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.
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Baseline and Week 72
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Phase 3: EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Visual Analogue Score (VAS) at Baseline and Week 72
기간: Baseline and Week 72
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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.
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Baseline and Week 72
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Phase 3: Number of Participants According to Response to Patient Global Impression of Severity (PGIS) Assessment at Baseline and at Week 30
기간: Baseline and Week 30
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PGIS is a single-item scale where participants rated the severity of colorectal cancer as follows: none, mild, moderate, severe and very severe.
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Baseline and Week 30
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Phase 3: Number of Participants According to Response to Patient Global Impression of Change (PGIC) Assessment at Week 30
기간: Week 30
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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.
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Week 30
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Phase 3: Trough Plasma Concentration of Encorafenib and Its Metabolite LHY746
기간: 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
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Trough plasma concentration of encorafenib and its metabolite LHY746 was measured in this outcome measure.
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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
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Phase 3: Cmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
기간: 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
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Cmax was observed directly from data.
LHY746 is a metabolite of Encorafenib.
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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
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Phase 3: AUC6 of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
기간: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5 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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Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5 and 6 hrs post-dose on Days 1 and 15 of Cycle 1
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Phase 3: AUCtau of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
기간: 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
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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.
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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
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Phase 3: Tmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
기간: 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
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Tmax: time (hours) to Cmax.
LHY746 is a metabolite of Encorafenib.
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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
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Phase 3: CL/F of Encorafenib in Mainland China Participants
기간: 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
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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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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
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Phase 3: Number of Participants Classified According to Microsatellite Instability (MSI) Status as Determined by Retrospective Central Testing of Baseline Tumor Tissue
기간: Baseline
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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.
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Baseline
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Phase 3: Number of Participants According to Circulating Tumor Deoxyribonucleic Acid (ctDNA) Status
기간: 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)
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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.
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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)
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Phase 3: Number of Participants According to B-Raf Serine/Threonine-Protein Kinase (BRAF) Valine 600 (V600) Status From ctDNA
기간: 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)
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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.
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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)
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Cohort 3: PFS as Assessed by BICR - FAS
기간: From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first
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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 by BICR or death or censoring date, whichever occurred first
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Cohort 3: ORR by Derived Investigator Assessment - FAS
기간: 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.
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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 14.1 months)
|
|
Cohort 3: DOR as Assessed by BICR - FAS
기간: 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
기간: 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
기간: From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first
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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 randomization to earliest documentation of PD or death or censoring date, whichever occurred first
|
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Cohort 3: OS - FAS
기간: 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.
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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
기간: 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.
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From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
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Cohort 3: TTR by Derived Investigator Assessment - FAS
기간: 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])
|
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Cohort 3: Number of Participants With AEs
기간: 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
|
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Cohort 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
기간: 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
|
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Cohort 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
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Cohort 3: Number of Participants According to BRAF V600 Status From ctDNA
기간: 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
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
스폰서
수사관
- 연구 책임자: Pfizer CT.gov Call Center, Pfizer
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- 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.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2020년 12월 21일
기본 완료 (실제)
2025년 3월 1일
연구 완료 (추정된)
2027년 12월 28일
연구 등록 날짜
최초 제출
2020년 10월 5일
QC 기준을 충족하는 최초 제출
2020년 10월 22일
처음 게시됨 (실제)
2020년 10월 29일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 6월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 5월 15일
마지막으로 확인됨
2026년 5월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 부위별 신생물
- 신생물
- 위장병
- 소화기계 질환
- 결장 질환
- 직장 신생물
- 대장 신생물
- 대장 신생물
- 위장관 신생물
- 장 신생물
- 장 질환
- 소화계 신생물
- 직장 질환
- 아미노산, 펩티드 및 단백질
- 단백질
- 유기 화학 물질
- 이종 사이 클릭 화합물, 1- 링
- 이종 사이 클릭 화합물
- 이종 사이 클릭 화합물, 2- 링
- 이종 사이 클릭 화합물, 융합 링
- 핵산, 뉴클레오티드 및 뉴 클레오 시드
- Camptothecin
- 알칼로이드
- 효소 및 코엔자임
- 항체, 모노클로 날, 인간화
- 항체, 모노클로 날
- 항체
- 면역 글로불린
- 면역 단백질
- 혈액 단백질
- 혈청 글로불린
- 글로불린
- 조정 복합체
- 데 옥시 시티 딘
- 시티 딘
- 피리 미딘 뉴 클레오 시드
- 피리 미딘
- 뉴 클레오 시드
- Formyltetrahydrofolates
- 테트라 하이드로 폴 레이트
- 엽산
- Pterins
- Teridines
- 우라실
- 피리 미디 논
- 코엔자임
- 데 옥시 리보 뉴 클레오 시드
- 카페시타빈
- 옥살리플라틴
- 베바시주맙
- 이리노테칸
- 세툭시맙
- 플루오로우라실
- 류코보린
- 레보류코보린
- Encorafenib
기타 연구 ID 번호
- C4221015
- BREAKWATER (기타 식별자: Pfizer)
- 2023-509405-77-00 (레지스트리 식별자: CTIS (EU))
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
예
IPD 계획 설명
화이자는 식별되지 않은 개별 참가자 데이터 및 관련 연구 문서(예:
프로토콜, 통계 분석 계획(SAP), 임상 연구 보고서(CSR)) 자격을 갖춘 연구자의 요청에 따라 특정 기준, 조건 및 예외가 적용됩니다.
화이자의 데이터 공유 기준 및 액세스 요청 프로세스에 대한 자세한 내용은 https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests에서 확인할 수 있습니다.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
예
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .