以前に未治療の転移性結腸直腸癌患者における化学療法の有無にかかわらず、エンコラフェニブとセツキシマブの併用に関する研究
2026年5月15日 更新者：Pfizer
転移性 BRAF V600E 変異型共同直腸 C の参加者を対象とした、エンコラフェニブとセツキシマブと化学療法の安全性のリードインを伴う、化学療法を併用する、または併用しないファーストラインのエンコラフェニブとセツキシマブの併用を比較した非盲検、マルチセンター、無作為化第 3 相試験
この研究の目的は、結腸直腸癌の潜在的な治療法として、単独で、または標準的な化学療法と併用して摂取した 2 つの治験薬 (encorafenib とセツキシマブ) を評価することです。
- 体の他の部分に広がっている (転移性);
- 「BRAF」と呼ばれるある種の異常な遺伝子を持っています。と
- 前治療を受けていない。
この研究の参加者は、次の研究治療のいずれかを受けます。
- エンコラフェニブとセツキシマブ：これらの参加者は、自宅で毎日経口でエンコラフェニブを受け取り、研究クリニックで静脈内（IV）注入（静脈への注射）によってセツキシマブを2週間に1回受け取ります。
- Encorafenib + セツキシマブと化学療法: これらの参加者は、上記の方法で encorafenib とセツキシマブを受け取ります。 さらに、彼らは自宅でIV注入と経口治療による標準的な化学療法を受けます。
- 化学療法のみ：これらの参加者は、この状態の標準治療である化学療法を、研究クリニックでのIV注入および自宅での経口治療によって受けます。
研究チームは、各参加者が研究治療にどのように反応するかを最大約3年間監視します。
調査の概要
状態
積極的、募集していない
条件
詳細な説明
この研究の目的は、エンコラフェニブとセツキシマブ（EC）を単独で、または化学療法と組み合わせて使用することで、未治療の BRAF V600E 変異 mCRC 患者の現在の標準的な化学療法と比較して臨床転帰を改善できるかどうかを評価することです。
encorafenib は以前に化学療法と併用されたことがないため、mFOLFOX6 と組み合わせた EC および FOLFIRI と組み合わせた EC の忍容性と PK は、どの化学療法の組み合わせが適切かを特定するために、試験の安全性の導入部分で別々のコホートで評価されます。試験のフェーズ 3 部分で使用されます。
研究の種類
介入
入学 (実際)
841
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
-
-
Arizona
-
Phoenix、Arizona、アメリカ、85054
- Mayo Clinic Hospital
-
Scottsdale、Arizona、アメリカ、85259
- Mayo Clinic in Arizona - Scottsdale
-
-
California
-
Los Angeles、California、アメリカ、90033
- USC / Norris Comprehensive Cancer Center
-
Los Angeles、California、アメリカ、90033
- USC/Norris Comprehensive Cancer Center
-
Los Angeles、California、アメリカ、90033
- Keck Hospital of USC
-
Los Angeles、California、アメリカ、90033
- LAC & USC Medical Center
-
Los Angeles、California、アメリカ、90033
- USC/Norris Comprehensive Cancer Center/Investigational Drug Services
-
Pasadena、California、アメリカ、91105
- Keck Hospital of USC Pasadena
-
-
Florida
-
Aventura、Florida、アメリカ、33180
- Mount Sinai Comprehensive Cancer Center, Aventura
-
Miami Beach、Florida、アメリカ、33140
- Mount Sinai Medical Center
-
Miami Beach、Florida、アメリカ、33140
- Mount Sinai Comprehensive Cancer Center
-
Plantation、Florida、アメリカ、33322
- BRCR Medical Center Inc.
-
Plantation、Florida、アメリカ、33322
- BRCR Global
-
-
Illinois
-
Chicago、Illinois、アメリカ、60637
- University Of Chicago Medical Center
-
Chicago、Illinois、アメリカ、60611
- UChicago Medicine - River East
-
Flossmoor、Illinois、アメリカ、60422
- UChicago Medicine at Ingalls - Flossmoor
-
Harvey、Illinois、アメリカ、60426
- UChicago Medicine Ingalls Memorial
-
New Lenox、Illinois、アメリカ、60451
- University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
-
Orland Park、Illinois、アメリカ、60462
- The University of Chicago Medicine Center for Advanced Care Orland Park
-
Tinley Park、Illinois、アメリカ、60477
- UChicago Medicine at Ingalls - Tinley Park
-
-
Louisiana
-
New Orleans、Louisiana、アメリカ、70121
- Ochsner Clinic Foundation
-
-
Minnesota
-
Rochester、Minnesota、アメリカ、55905
- Mayo Clinic Rochester
-
-
Missouri
-
City of Saint Peters、Missouri、アメリカ、63376
- Siteman Cancer Center - St Peters
-
Creve Coeur、Missouri、アメリカ、63141
- Siteman Cancer Center - West County
-
Florissant、Missouri、アメリカ、63031
- Siteman Cancer Center - North County
-
St Louis、Missouri、アメリカ、63110
- Washington University School of Medicine
-
St Louis、Missouri、アメリカ、63129
- Siteman Cancer Center - South County
-
St Louis、Missouri、アメリカ、63110
- Barnes- Jewish Hospital
-
-
Nebraska
-
Omaha、Nebraska、アメリカ、68130
- Oncology Hematology West PC dba Nebraska Cancer Specialists
-
Omaha、Nebraska、アメリカ、68124
- Oncology Hematology West PC dba Nebraska Cancer Specialists
-
Omaha、Nebraska、アメリカ、68114
- Oncology Hematology West PC dba Nebraska Cancer Specialists
-
Papillion、Nebraska、アメリカ、68046
- Oncology Hematology West PC dba Nebraska Cancer Specialists
-
-
New Jersey
-
Basking Ridge、New Jersey、アメリカ、07920
- Memorial Sloan Kettering Cancer Center - Basking Ridge
-
Berkeley Heights、New Jersey、アメリカ、07922
- Summit Medical Group
-
Florham Park、New Jersey、アメリカ、07932
- Summit Medical Group
-
Middletown、New Jersey、アメリカ、07748
- Memorial Sloan Kettering Cancer Center- Monmouth
-
Montvale、New Jersey、アメリカ、07645
- Memorial Sloan Kettering Cancer Center- Bergen
-
-
New York
-
Commack、New York、アメリカ、11725
- Memorial Sloan Kettering Cancer Center Commack
-
Harrison、New York、アメリカ、10604
- Memorial Sloan Kettering Cancer Center - Westchester
-
New York、New York、アメリカ、10022
- Memorial Sloan Kettering Cancer Center
-
New York、New York、アメリカ、10065
- Memorial Sloan Kettering Cancer Center - Main Campus
-
Uniondale、New York、アメリカ、11553
- Memorial Sloan Kettering Cancer Center- Nassau
-
-
Ohio
-
Cleveland、Ohio、アメリカ、44195
- Cleveland Clinic
-
Cleveland、Ohio、アメリカ、44195
- Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
-
Columbus、Ohio、アメリカ、43221
- Martha Morehouse Medical plaza
-
Columbus、Ohio、アメリカ、43210
- The Ohio State University James Cancer Hospital and Solove Research Institute
-
Columbus、Ohio、アメリカ、43212
- Stefanie Spielman Comprehensive Breast Cancer
-
Columbus、Ohio、アメリカ、43210
- The Ohio State University Wexner Medical Center Investigational Drug Services
-
-
Oklahoma
-
Oklahoma City、Oklahoma、アメリカ、73104
- University of Oklahoma Health Sciences Center, OU Health Stephenson Cancer Center
-
-
Oregon
-
Portland、Oregon、アメリカ、97213
- Providence Cancer Institute Franz Clinic
-
Portland、Oregon、アメリカ、97213
- Providence Portland Medical Center
-
Portland、Oregon、アメリカ、97225
- Providence St Vincent Medical Center
-
Portland、Oregon、アメリカ、97225
- Providence Onc and Heme Care Clinic - Westside
-
-
Pennsylvania
-
Pittsburgh、Pennsylvania、アメリカ、15232
- UPMC Hillman Cancer Center
-
-
Tennessee
-
Germantown、Tennessee、アメリカ、38138
- The West Clinic. PLLC. dba West Cancer Center
-
Nashville、Tennessee、アメリカ、37232
- Vanderbilt-Ingram Cancer Center
-
Nashville、Tennessee、アメリカ、37232
- Henry-Joyce Cancer Clinic
-
-
Texas
-
Houston、Texas、アメリカ、77030
- The University of Texas MD Anderson Cancer Center
-
-
Virginia
-
Richmond、Virginia、アメリカ、23219
- Virginia Commonwealth University
-
-
Washington
-
Seattle、Washington、アメリカ、98109
- Seattle Cancer Care Alliance
-
Seattle、Washington、アメリカ、98195
- University of Washington Medical Center
-
-
Wisconsin
-
Madison、Wisconsin、アメリカ、53792
- University of Wisconsin Clinical Science Center
-
-
-
-
-
Buenos Aires、アルゼンチン、1426
- Instituto Medico Especializado Alexander Fleming
-
Córdoba、アルゼンチン、X5004FHP
- Clínica Universitaria Reina Fabiola
-
Córdoba、アルゼンチン、X5016KEH
- Hospital Privado Centro Medico de Cordoba
-
-
Tucumán Province
-
San Miguel de Tucumán、Tucumán Province、アルゼンチン、4000
- Centro Medico San Roque
-
-
-
-
-
Birmingham、イギリス、B9 5SS
- Heartlands Hospital
-
London、イギリス、W12 0HS
- Hammersmith Hospital, Imperial College Healthcare NHS Trust
-
London、イギリス、W6 8RF
- Hammersmith Hospital
-
Oxford、イギリス、OX3 7LE
- Churchill Hospital - Oncology
-
-
HIGH Heaton
-
Newcastle upon Tyne、HIGH Heaton、イギリス、NE7 7DN
- Freeman Hospital
-
-
Surrey
-
Sutton、Surrey、イギリス、SM2 5PT
- Royal Marsden NHS Foundation Trust
-
-
-
-
-
Brescia、イタリア、25124
- Fondazione Poliambulanza Istituto Ospedaliero
-
Milan、イタリア、20141
- Istituto Europeo di Oncologia IRCCS
-
Naples、イタリア、80131
- Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" di Napoli
-
Padova、イタリア、35128
- IRCCS Istituto Oncologico Veneto (IOV)
-
Reggio Emilia、イタリア、42123
- Azienda USL - IRCCS di Reggio Emilia - Arcispedale Santa Maria Nuova
-
-
Cagliari
-
Monserrato (CA)、Cagliari、イタリア、09042
- Azienda Ospedaliera Universitaria di Cagliari - Presidio Policlinico Universitario "D.Casula"
-
-
Foggia
-
San Giovanni Rotondo、Foggia、イタリア、71013
- IRCCS Casa Sollievo della Sofferenza
-
-
Milano
-
Milan、Milano、イタリア、20162
- ASST Grande Ospedale Metropolitano Niguarda
-
-
Torino
-
Candiolo、Torino、イタリア、10060
- Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo IRCCS
-
Orbassano、Torino、イタリア、10043
- Azienda Ospedaliero Universitaria San Luigi Gonzaga
-
-
-
-
Maharashtra
-
Mumbai、Maharashtra、インド、400012
- Tata Memorial Hospital
-
Pune、Maharashtra、インド、411 004
- Deenanath Mangeshkar Hospital & Research Centre
-
Pune、Maharashtra、インド、411 004
- Sahyadri Speciality Hospital
-
Thane、Maharashtra、インド、401107
- Bhakti Vedanta Hospital and Research Institute
-
-
National Capital Territory of Delhi
-
New Delhi、National Capital Territory of Delhi、インド、110085
- Rajiv Gandhi Cancer Institute And Research Centre
-
-
Rajasthan
-
Jaipur、Rajasthan、インド、302004
- Sawai Man Singh Medical College Hospital (SMS Hospital)
-
-
-
-
-
Dnipro、ウクライナ、49102
- Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
-
Ivano-Frankivsk、ウクライナ、76018
- Ivano-Frankivsk National Medical University
-
Ivano-Frankivsk、ウクライナ、76018
- MNPE "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Regional Council"
-
Kryvyi Rih、ウクライナ、50048
- Communal enterprise "Kryvyi Rih Oncology Dispensary" of Dnipropetrovsk Regional Council
-
-
-
-
-
Utrecht、オランダ、3584 CX
- Universitair Medisch Centrum Utrecht
-
-
North Brabant
-
Eindhoven、North Brabant、オランダ、5623 EJ
- Catharina Ziekenhuis
-
-
North Holland
-
Amsterdam、North Holland、オランダ、1066 CX
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
-
-
-
-
New South Wales
-
Camperdown、New South Wales、オーストラリア、2050
- Chris O'Brien Lifehouse
-
Liverpool、New South Wales、オーストラリア、2170
- Liverpool Hospital
-
St Leonards、New South Wales、オーストラリア、2065
- GenesisCare North Shore
-
St Leonards、New South Wales、オーストラリア、2065
- GenesisCare - North Shore
-
-
Queensland
-
Herston、Queensland、オーストラリア、4029
- Royal Brisbane and Women's Hospital
-
Woolloongabba、Queensland、オーストラリア、4102
- Princess Alexandra Hospital
-
-
South Australia
-
Adelaide、South Australia、オーストラリア、5011
- The Queen Elizabeth Hospital
-
Adelaide、South Australia、オーストラリア、5000
- Central Adelaide Local Health Network Incorporated
-
-
Victoria
-
Clayton、Victoria、オーストラリア、3168
- Monash Health
-
Heidelberg、Victoria、オーストラリア、3084
- Austin Health
-
Melbourne、Victoria、オーストラリア、3000
- Peter MacCallum Cancer Centre
-
Melbourne、Victoria、オーストラリア、3004
- Alfred Health
-
-
-
-
Alberta
-
Calgary、Alberta、カナダ、T2N 4N2
- Alberta Health Services - Cancer Care, Tom Baker Cancer Centre
-
Calgary、Alberta、カナダ、T3N 4N1
- Arthur J.E. Child Comprehensive Cancer Centre
-
Edmonton、Alberta、カナダ、T6G 1Z2
- Cross Cancer Institute
-
Edmonton、Alberta、カナダ、T6G 2C8
- Alberta Health Services and The Governors of The University of Alberta
-
-
Ontario
-
London、Ontario、カナダ、N6A 5W9
- London Regional Cancer Program, London Health Sciences Centre
-
Toronto、Ontario、カナダ、M4N 3M5
- Sunnybrook Health Sciences Centre
-
-
Quebec
-
Montreal、Quebec、カナダ、H3T 1E2
- Jewish General Hospital
-
-
-
-
-
Stockholm、スウェーデン、171 76
- Department of Pelvic cancer, colorecta section, Karolinska University Hospital
-
-
Stockholms LÄN [se-01]
-
Solna、Stockholms LÄN [se-01]、スウェーデン、171 64
- Karolinska Universitetssjukhuset Solna
-
-
Uppsala LÄN [se-03]
-
Uppsala、Uppsala LÄN [se-03]、スウェーデン、751 85
- Akademiska Sjukhuset
-
-
Västerbottens LÄN [se-24]
-
Umeå、Västerbottens LÄN [se-24]、スウェーデン、90185
- Norrlands universitetssjukhus
-
-
Västra Götalands LÄN [se14]
-
Gothenburg、Västra Götalands LÄN [se14]、スウェーデン、413 45
- Sahlgrenska Universitetssjukhuset
-
-
-
-
-
Barcelona、スペイン、08035
- Hospital Universitario Vall d'Hebron
-
Barcelona、スペイン、08036
- Hospital Clinic Barcelona
-
Madrid、スペイン、28034
- Hospital Universitario Ramon y Cajal
-
Madrid、スペイン、28041
- Hospital Universitario 12 de Octubre
-
Madrid、スペイン、28007
- Hospital General Universitario Gregorio Marañón
-
Seville、スペイン、41013
- Hospital Universitario Virgen del Rocío
-
Valencia、スペイン、46010
- Hospital Clínico Universitario de Valencia
-
Valencia、スペイン、46014
- Hospital General Universitario de Valencia
-
Zaragoza、スペイン、50009
- Hospital Universitario Miguel Servet
-
-
A Coruña
-
Santiago de Compostela、A Coruña、スペイン、15706
- Complejo Hospitalario Universitario Santiago de Compostela
-
-
Alicante
-
Elche、Alicante、スペイン、03203
- Hospital General Universitario de Elche
-
-
Barcelona
-
L'Hospitalet de Llobregat、Barcelona、スペイン、08908
- ICO L'Hospitalet (Hospital Duran i Reynals)
-
-
-
-
-
Bratislava、スロバキア、833 10
- Narodny onkologicky ustav
-
Košice、スロバキア、04191
- Vychodoslovensky onkologicky ustav, a.s.
-
-
-
-
-
Olomouc、チェコ、779 00
- Fakultni Nemocnice Olomouc
-
Prague、チェコ、180 81
- Fakultní nemocnice Bulovka
-
-
Brno-město
-
Brno、Brno-město、チェコ、625 00
- Fakultní nemocnice Brno Bohunice
-
-
Hradec Králové
-
Hradec Králové、Hradec Králové、チェコ、500 05
- Fakultni nemocnice Hradec Kralove
-
-
Praha 4
-
Prague、Praha 4、チェコ、14059
- Fakultni Thomayerova nemocnice
-
-
-
-
-
Copenhagen、デンマーク、2100
- Rigshospitalet
-
Herlev、デンマーク、2730
- Herlev and Gentofte Hospital
-
Odense C、デンマーク、5000
- Odense University Hospital
-
-
North Denmark
-
Aalborg、North Denmark、デンマーク、9000
- Aalborg Universitetshospital, Syd
-
-
Region Syddanmark
-
Vejle、Region Syddanmark、デンマーク、7100
- Vejle Sygehus
-
Vejle、Region Syddanmark、デンマーク、7100
- Vejle Hospital-Sygehus Lillebaelt
-
-
-
-
-
Berlin、ドイツ、10707
- Onkologische Schwerpunktpraxis Kurfuerstendamm
-
Berlin、ドイツ、13125
- HELIOS Klinikum Berlin Buch GmbH
-
Charlottenburg、ドイツ、10719
- Radiologie Berlin
-
Dresden、ドイツ、01307
- Universitätsklinikum Carl Gustav Carus Dresden
-
Dresden、ドイツ、01307
- Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus
-
Hamburg、ドイツ、20249
- Facharztzentrum Eppendorf
-
Hamburg、ドイツ、22045
- ZytoService Deutschland GmbH, Standort-Hamburg-Jenfeld
-
Hamburg、ドイツ、22297
- Radiologie im Israelitischen Krankenhaus
-
-
Bavaria
-
Munich、Bavaria、ドイツ、81737
- Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
-
-
Hesse
-
Frankfurt am Main、Hesse、ドイツ、60488
- Institut für Klinisch Onkologische Forschung
-
-
Lower Saxony
-
Hanover、Lower Saxony、ドイツ、30625
- Medizinische Hochschule Hannover
-
-
Saxony
-
Leipzig、Saxony、ドイツ、04103
- Universitatsklinikum Leipzig
-
-
-
-
-
Auckland、ニュージーランド、1023
- Auckland City Hospital
-
-
-
-
-
Oslo、ノルウェー、0379
- Oslo universitetssykehus, Radiumhospitalet
-
Oslo、ノルウェー、0450
- Oslo Universitetssykehus Ullevål
-
-
Sør-trøndelag
-
Trondheim、Sør-trøndelag、ノルウェー、7030
- St. Olavs Hospital
-
-
Vest-agder
-
Kristiansand、Vest-agder、ノルウェー、N-4615
- Sørlandet Sykehus Kristiansand
-
-
-
-
-
Oulu、フィンランド、90220
- Oulu University Hospital
-
Pori、フィンランド、28500
- Satakunnan Keskussairaala
-
Tampere、フィンランド、33521
- Tampereen yliopistollinen sairaala
-
Tampere、フィンランド、33520
- Tampereen yliopistollinen sairaala
-
Turku、フィンランド、20520
- Turku University Hospital
-
-
Southwest Finland
-
Turku、Southwest Finland、フィンランド、20520
- Turku University Hospital
-
-
Uusimaa
-
Helsinki、Uusimaa、フィンランド、00290
- Helsinki University Central Hospital
-
Helsinki、Uusimaa、フィンランド、00180
- Docrates Syöpäsairaala
-
-
-
-
Rio Grande do Sul
-
Porto Alegre、Rio Grande do Sul、ブラジル、90035-903
- Hospital de Clinicas de Porto Alegre
-
-
Rio de Janeiro
-
Rio de Janeiro、Rio de Janeiro、ブラジル、20230-130
- Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
-
-
Santa Catarina
-
Blumenau、Santa Catarina、ブラジル、89010-340
- Reichow - Centro de Ensino e Pesquisa
-
Itajaí、Santa Catarina、ブラジル、88301-220
- Clinica de Neoplasias Litoral
-
-
São Paulo
-
Barretos、São Paulo、ブラジル、14784400
- Fundacao Pio XII - Hospital de Cancer de Barretos
-
Barretos、São Paulo、ブラジル、14.780-070
- Fundacao Pio XII - Hospital de Cancer de Barretos
-
Santo André、São Paulo、ブラジル、09060-650
- CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
-
Santo André、São Paulo、ブラジル、09060-870
- FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Onco
-
São José do Rio Preto、São Paulo、ブラジル、15090000
- Fundação Faculdade Regional de Medicina de São José do Rio Preto
-
-
-
-
-
Gabrovo、ブルガリア、5300
- MHAT "Dr. Tota Venkova" AD
-
Plovdiv、ブルガリア、4000
- MHAT Central Onco Hospital OOD
-
Plovdiv、ブルガリア、4004
- Complex Oncology Center - Plovdiv EOOD
-
Sofia、ブルガリア、1303
- Medical Center Nadezhda Clinical EOOD
-
Sofia、ブルガリア、1407
- Acibadem City Clinic MHAT Tokuda
-
Sofia、ブルガリア、1750
- University Multiprofile Hospital for Active Treatment Sofiamed
-
-
Pazardzhik
-
Panagyurishte、Pazardzhik、ブルガリア、4500
- MHAT Uni Hospital OOD
-
-
-
-
-
Antwerp、ベルギー、2020
- ZNA Middelheim
-
Leuven、ベルギー、3000
- UZ Leuven
-
Liège、ベルギー、4000
- Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
-
Wilrijk、ベルギー、2610
- ZAS Augustinus
-
-
Bruxelles-capitale, Région de
-
Brussels、Bruxelles-capitale, Région de、ベルギー、1070
- Université Libre de Bruxelles - Hôpital Erasme
-
Brussels、Bruxelles-capitale, Région de、ベルギー、1200
- Cliniques universitaires Saint-Luc
-
-
Hainaut
-
Charleroi、Hainaut、ベルギー、6060
- Grand Hôpital de Charleroi
-
-
West-vlaanderen
-
Kortrijk、West-vlaanderen、ベルギー、8500
- AZ Groeninge Campus Kennedylaan
-
-
-
-
-
Brzozów、ポーランド、36-200
- Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
-
Bytom、ポーランド、41-902
- Wojewodzki Szpital Specjalistyczny Nr 4 w Bytomiu Oddzial Onkologii
-
Gdansk、ポーランド、80-219
- Copernicus Podmiot Leczniczy Sp. z o.o. Wojewódzkie Centrum Onkologii
-
Gdansk、ポーランド、80-219
- COPERNICUS PL sp. z. o. o. Wojewodzkie Centrum Onkologii w Gdansku Ambulatoryjna
-
-
Greater Poland Voivodeship
-
Konin、Greater Poland Voivodeship、ポーランド、62-500
- Przychodnia Lekarska KOMED
-
-
-
-
-
Oaxaca City、メキシコ、68020
- Centro de Investigacion Clinica de Oaxaca
-
-
Nuevo León
-
Monterrey、Nuevo León、メキシコ、64000
- Accelerium, S. de R.L. de C.V.
-
-
-
-
-
Chelyabinsk、ロシア、454087
- GBUZ
-
Kaluga、ロシア、248007
- Kaluga Regional Clinical Oncology Center
-
Moscow、ロシア、119991
- FSAEI HE I.M Sechenov First MSMU MoH Russia (Sechenovskiy University),
-
Omsk、ロシア、644013
- BHI of Omsk region "Clinical Oncology Dispensary"
-
Omsk、ロシア、644046
- BHI of Omsk region "Clinical Oncology Dispensary"
-
Saint Petersburg、ロシア、191025
- LLC "Medicina Severnoy Stolitsy"
-
Saint Petersburg、ロシア、192007
- LLC "Severo-Zapadny Medical Center"
-
Saint Petersburg、ロシア、195271
- Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg
-
Saint Petersburg、ロシア、197022
- LLC "Eurocityclinic"
-
Saint Petersburg、ロシア、197758
- FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov
-
Yaroslavl、ロシア、150054
- SHI YR Regional Clinical Oncology Hospital
-
-
Sankt-Peterburg
-
Pushkin、Sankt-Peterburg、ロシア、196603
- Private Medical Institution "Euromedservice"
-
-
-
-
-
Shanghai、中国、201321
- Fudan University Shanghai Cancer Center
-
Tianjin、中国、300000
- Tianjin Union Medical Center
-
-
Beijing Municipality
-
Beijing、Beijing Municipality、中国、100142
- Beijing Cancer Hospital
-
Beijing、Beijing Municipality、中国、100034
- Peking University First Hospital
-
Beijing、Beijing Municipality、中国、100730
- Beijing Hospital
-
Beijing、Beijing Municipality、中国、100021
- Cancer Hospital Chinese Academy of Medical Science
-
-
Chongqing Municipality
-
Chongqing、Chongqing Municipality、中国、400030
- Chongqing University Cancer Hospital
-
-
Fujian
-
Fuzhou、Fujian、中国、350001
- Fujian Medical University Union Hospital
-
-
Guangdong
-
Guangzhou、Guangdong、中国、510655
- The Sixth Affiliated Hospital of Sun Yat-sen University
-
-
Guangxi
-
Nanning、Guangxi、中国、530200
- Affiliated Tumor Hospital of Guangxi Medical University
-
-
Hubei
-
Wuhan、Hubei、中国、430030
- Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
-
-
Hunan
-
Changsha、Hunan、中国、410013
- The Third XIANGYA Hospital of Central South University
-
Changsha、Hunan、中国、410011
- The Second Xiangya Hospital of Central South University
-
-
Jiangsu
-
Nanjing、Jiangsu、中国、210008
- Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
-
-
Liaoning
-
Shenyang、Liaoning、中国、110022
- Shengjing Hospital of China Medical University
-
-
Shandong
-
Jinan、Shandong、中国、250117
- Shandong province cancer hospital
-
-
Shanghai Municipality
-
Shanghai、Shanghai Municipality、中国、200080
- Shanghai General Hospital
-
Shanghai、Shanghai Municipality、中国、201800
- Ruijin Hospital Shanghai Jiaotong University School of Medicine
-
-
Sichuan
-
Chengdu、Sichuan、中国、610041
- Sichuan province cancer hospital
-
-
Yunnan
-
Kunming、Yunnan、中国、650118
- Yunnan Cancer Hospital(The Third Affiliated Hospital of Kunming Medical University)
-
-
Zhejiang
-
Hangzhou、Zhejiang、中国、310000
- The second Affiliated Hospital of College of Medicine, Zhejiang University
-
-
-
-
-
Johannesburg、南アフリカ、2193
- Wits Health Consortium (Pty) Ltd
-
-
CAPE TOWN
-
Rondebosch、CAPE TOWN、南アフリカ、7700
- Cancercare Rondebosch Oncology
-
-
Eastern Cape
-
Port Elizabeth、Eastern Cape、南アフリカ、6045
- Cancercare Langenhoven Drive Oncology Centre
-
-
-
-
-
Kaohsiung City、台湾、807
- Kaohsiung Medical University Chung-Ho Memorial Hospital
-
Taichung、台湾、404
- China Medical University Hospital
-
Tainan、台湾、704
- National Cheng-Kung University Hospital
-
Tainan、台湾、73657
- Chi Mei Hospital, Liouying
-
Taipei、台湾、100
- National Taiwan University Hospital
-
Taipei、台湾、11031
- Taipei Medical University Hospital
-
Taipei、台湾、112
- Taipei Veterans General Hospital
-
Taoyuan、台湾、333
- Chang Gung Medical Foundation-Linkou Branch
-
-
-
-
-
Fukuoka、日本、811-1395
- National Hospital Organization Kyushu Cancer Center
-
Osaka、日本、540-0006
- National Hospital Organization - Osaka National Hospital - Institute For Clinical Research
-
-
Chiba
-
Chiba、Chiba、日本、260-8717
- Chiba Cancer Center
-
Kashiwa、Chiba、日本、277-8577
- National Cancer Center Hospital East
-
-
Hokkaido
-
Sapporo、Hokkaido、日本、060-8648
- Hokkaido University Hospital
-
-
Ishikawa-ken
-
Kanazawa、Ishikawa-ken、日本、920-8641
- Kanazawa University Hospital
-
-
Kanagawa
-
Kawasaki、Kanagawa、日本、216-8511
- St. Marianna University Hospital
-
Yokohama、Kanagawa、日本、2418515
- Kanagawa Cancer Center
-
-
Nagoya, Aichi
-
Nagoya、Nagoya, Aichi、日本、464-8681
- Aichi Cancer Center Hospital
-
-
Osaka
-
Osaka、Osaka、日本、5418567
- Osaka Prefectural Hospital Organization Osaka International Cancer Institute
-
Sayama、Osaka、日本、589-8511
- Kindai University Hospital
-
Suita、Osaka、日本、565-0871
- Osaka University Hospital
-
Takatsuki、Osaka、日本、569-8686
- Osaka Medical and Pharmaceutical University Hospital
-
-
Saitama
-
Hidaka、Saitama、日本、350-1298
- Saitama Medical University International Medical Center
-
Ina-machi、Saitama、日本、362-0806
- Saitama Prefectural Cancer Center
-
-
Shizuoka
-
Nakatogari、Shizuoka、日本、411-8777
- Shizuoka Cancer Center
-
-
Tokyo
-
Chuo-ku、Tokyo、日本、104-0045
- National Cancer Center Hospital
-
Koto-ku、Tokyo、日本、135-8550
- The Cancer Institute Hospital of JFCR
-
Shinjuku-ku、Tokyo、日本、160-8582
- Keio University Hospital
-
-
-
-
-
Busan、韓国、49201
- Dong-A University Hospital
-
Daegu、韓国、41404
- Kyungpook National University Chilgok Hospital
-
Incheon、韓国、21565
- Gachon University Gil Medical Center
-
Seoul、韓国、03080
- Seoul National University Hospital
-
Seoul、韓国、05505
- Asan Medical Center
-
Seoul、韓国、06351
- Samsung Medical Center
-
Seoul、韓国、03722
- Severance Hospital, Yonsei University Health System
-
Seoul、韓国、02841
- Korea University Anam Hospital
-
-
Gyeonggi-do
-
Goyang-si、Gyeonggi-do、韓国、10408
- National Cancer Center
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
16年歳以上 (子、大人、高齢者)
健康ボランティアの受け入れ
いいえ
説明
包含基準:
- Safety Lead-In = 18 歳以上の男性/女性
- フェーズ 3: 16 歳以上の男性/女性 (現地で許可されている場合)
- -組織学的または細胞学的に確認された、BRAF V600E変異を含むステージIVのCRC
- 転移性設定における以前の全身治療
- SLI: 0-1 レジメン
- フェーズ 3: なし
- -以前のアジュバントまたはネオアジュバント療法は、再発/転移がアジュバント/ネオアジュバント治療の終了から6か月未満の場合、転移治療と見なされました
- 測定可能な疾患 (フェーズ 3)/測定可能なまたは評価可能な疾患 (安全性の導入)
- ECOG PS 0-1
- 適切な臓器機能
除外基準:
- -局所的に確認された、または未知のMSI-HまたはdMMRである腫瘍 参加者が既存の病状のために免疫チェックポイント阻害剤を受け取る資格がない場合を除きます
- -投与開始前の2週間の活動的な細菌またはウイルス感染
- 症候性脳転移
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：安全導入コホート 1
エンコラフェニブ 300 mg を 1 日 1 回経口投与 セツキシマブ 500 mg/m2 (120 分間の点滴静注) 2 週間ごと イリノテカン 180 mg/m2 (90 分間の点滴静注) 2 週間ごと ロイコボリン 400 mg/m2 (120 分間の点滴静注) 2 週間ごと週 5-FU 400 mg/m2 IV ボーラス、その後 5-FU 2400 mg/m2 を 46 ～ 48 時間かけて 2 週間ごとに連続 IV 注入
|
75mgカプセル
他の名前：
静脈注射用 100 mg/バイアル、200 mg/バイアル、または 500 mg/バイアル
他の名前：
点滴用溶液 40 mg/バイアル、100 mg/バイアル、または 300 mg/バイアル
他の名前：
注射 50 mg/バイアル、100 mg/バイアル、200 mg/バイアル、または 350 mg/バイアル
他の名前：
静脈注射用 250 mg/バイアル、500 mg/バイアル、または 1000 mg/バイアル
他の名前：
|
|
実験的：安全導入コホート 2
エンコラフェニブ 300 mg を 1 日 1 回経口投与 セツキシマブ 500 mg/m2 (120 分間の点滴静注) 2 週間ごと オキサリプラチン 85 mg/m2 (120 分間の点滴静注) 2 週間ごと5-FU 400 mg/m2 IV ボーラス、その後 5-FU 2400 mg/m2 持続 IV 注入を 46 ～ 48 時間かけて 2 週間ごとに
|
75mgカプセル
他の名前：
静脈注射用 100 mg/バイアル、200 mg/バイアル、または 500 mg/バイアル
他の名前：
注射 50 mg/バイアル、100 mg/バイアル、200 mg/バイアル、または 350 mg/バイアル
他の名前：
静脈注射用 250 mg/バイアル、500 mg/バイアル、または 1000 mg/バイアル
他の名前：
静脈内用溶液用粉末 50 mg/バイアル、100 mg/バイアル、または 200 mg/バイアル
他の名前：
|
|
実験的：フェーズ 3 アーム A
Encorafenib 300 mg を 1 日 1 回経口投与 セツキシマブ 500 mg/m2（120 分間の IV 注入）を 2 週間ごとに投与
|
75mgカプセル
他の名前：
静脈注射用 100 mg/バイアル、200 mg/バイアル、または 500 mg/バイアル
他の名前：
|
|
実験的：フェーズ 3 アーム B
エンコラフェニブ 300 mg を 1 日 1 回経口投与 セツキシマブ 500 mg/m2 (120 分間の点滴静注) 2 週間ごと オキサリプラチン 85 mg/m2 (120 分間の点滴静注) 2 週間ごと5-FU 400 mg/m2 IV ボーラス、その後 5-FU 2400 mg/m2 持続 IV 注入を 46 ～ 48 時間かけて 2 週間ごとに
|
75mgカプセル
他の名前：
静脈注射用 100 mg/バイアル、200 mg/バイアル、または 500 mg/バイアル
他の名前：
注射 50 mg/バイアル、100 mg/バイアル、200 mg/バイアル、または 350 mg/バイアル
他の名前：
静脈注射用 250 mg/バイアル、500 mg/バイアル、または 1000 mg/バイアル
他の名前：
静脈内用溶液用粉末 50 mg/バイアル、100 mg/バイアル、または 200 mg/バイアル
他の名前：
|
|
アクティブコンパレータ：フェーズ 3 アーム C
2 週間ごと: オキサリプラチン 85 mg/m2 (120 分間の静注) ロイコボリン 400 mg/m2 (120 分間の静注) 5-FU 400 mg/m2 の急速静注、その後 5-FU 2400 mg/m2 の持続的な静注46-48 時間 ベバシズマブ (オプション; 処方指示に従って投与) -または- 2 週間ごと: イリノテカン 165 mg/m2 (90 分間の IV 注入) オキサリプラチン 85 mg/m2 (120 分間の IV 注入) ロイコボリン 400 mg/m2 ( 5-FU 2400 または 3200 mg/m2 を 46 ～ 48 時間にわたって持続的に IV 注入 ベバシズマブ (オプション; 処方説明書に従って投与) -または- オキサリプラチン 130 mg/m2 (120 分間の IV 注入) 3 週間ごと カペシタビン1000 mg/m2 の経口錠剤を 1 日 2 回、1 日目から 14 日目にベバシズマブ (任意、処方説明書に従って投与)
|
点滴用溶液 40 mg/バイアル、100 mg/バイアル、または 300 mg/バイアル
他の名前：
注射 50 mg/バイアル、100 mg/バイアル、200 mg/バイアル、または 350 mg/バイアル
他の名前：
静脈注射用 250 mg/バイアル、500 mg/バイアル、または 1000 mg/バイアル
他の名前：
静脈内用溶液用粉末 50 mg/バイアル、100 mg/バイアル、または 200 mg/バイアル
他の名前：
150mgまたは500mgの錠剤
他の名前：
静脈内使用のためのオプションの注射 100 mg/バイアルまたは 400 mg/バイアル
他の名前：
|
|
実験的：コホート 3 アーム D
エンコラフェニブ 300 mg を 1 日 1 回経口投与 セツキシマブ 500 mg/m2 (120 分間の点滴静注) 2 週間ごと イリノテカン 180 mg/m2 (90 分間の点滴静注) 2 週間ごと ロイコボリン 400 mg/m2 (120 分間の点滴静注) 2 週間ごと週 5-FU 400 mg/m2 IV ボーラス、その後 5-FU 2400 mg/m2 を 46 ～ 48 時間かけて 2 週間ごとに連続 IV 注入
|
75mgカプセル
他の名前：
静脈注射用 100 mg/バイアル、200 mg/バイアル、または 500 mg/バイアル
他の名前：
点滴用溶液 40 mg/バイアル、100 mg/バイアル、または 300 mg/バイアル
他の名前：
注射 50 mg/バイアル、100 mg/バイアル、200 mg/バイアル、または 350 mg/バイアル
他の名前：
静脈注射用 250 mg/バイアル、500 mg/バイアル、または 1000 mg/バイアル
他の名前：
|
|
アクティブコンパレータ：コホート 3 アーム E
イリノテカン 180 mg/m2 (90 分間静注) 2 週間ごと、ロイコボリン 400 mg/m2 (120 分間静注) 2 週間ごと、5-FU 400 mg/m2 静注ボーラス、その後 5-FU 2400 mg/m2 2 週間ごとに 46 ～ 48 時間にわたる持続的な IV 注入、ベバシズマブ (オプション、処方指示に従って投与)
|
点滴用溶液 40 mg/バイアル、100 mg/バイアル、または 300 mg/バイアル
他の名前：
注射 50 mg/バイアル、100 mg/バイアル、200 mg/バイアル、または 350 mg/バイアル
他の名前：
静脈注射用 250 mg/バイアル、500 mg/バイアル、または 1000 mg/バイアル
他の名前：
静脈内使用のためのオプションの注射 100 mg/バイアルまたは 400 mg/バイアル
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
SLI: Number of Participants With Dose Limiting Toxicity (DLTs)
時間枠：Cycle 1 (28 days)
|
DLT: Any AE/lab value during first 28 days (D) of treatment that met at least 1 criteria: AE/lab value unrelated to underlying disease,PD,intercurrent illness,concomitant medications resulting in inability to tolerate atleast 75% of planned dose intensity of study drug,fatigue grade (G)3>14 consecutive D, interstitial lung disease G>=2,rash,hand foot skin reaction G3>14 consecutive D or G4,diarrhea G3 >=48 hours or G4,nausea/vomiting G3>=48 hours or G4,mucositis G>=3,total bilirubin G>=3, aspartate aminotransferase/alanine aminotransferase G>=3 in conjunction with total bilirubin G>=2 or G3 >7 consecutive D or G4,Serum creatinine G>=3,absolute neutrophil count G4 >7 consecutive D, >=G3 febrile neutropenia,G3 platelet count decreased with signs of bleeding,platelet count G4,ECG QTcF prolonged >=G3,G>=3 uveitis >21 consecutive D,G4 confirmed by ophthalmic examination,paresthesia/dysesthesias G>=3,other G>=3 hematologic/nonhematologic toxicity except lymphocyte count decreased G>=3.
|
Cycle 1 (28 days)
|
|
Phase 3: Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) for Arm B vs Arm C - FAS
時間枠：From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
PFS was defined as the time from date of randomization to earliest documented disease progression (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death due to any cause as assessed by BICR.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 millimeter (mm) for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: Objective Response Rate (ORR) as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset
時間枠：From date of randomization to until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 24.71 months)
|
ORR was defined as the percentage of participants who achieved best overall response (BOR) of confirmed complete response (CR) or partial response (PR) according to RECIST v 1.1 as assessed by BICR.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization to until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 24.71 months)
|
|
Cohort 3: ORR as Assessed by BICR for Arm D vs Arm E - FAS
時間枠：From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 14.1 months)
|
ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 as assessed by BICR.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 14.1 months)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
SLI: Number of Participants With Adverse Events (AEs)
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
An Serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event.
AEs included both SAEs and all non-SAEs.
|
Through end of the study
|
|
SLI: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention.
AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
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Through end of the study
|
|
SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
時間枠：Through end of the study
|
The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased.
Laboratory abnormalities were graded according to NCI CTCAE version 4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death.
Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
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Through end of the study
|
|
SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
時間枠：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.
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Through end of the study
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|
SLI: Number of Participants According to Categorization of Vital Signs Data
時間枠：Through end of the study
|
The criteria for vital signs included: Systolic blood pressure (millimeters of mercury [mmHg]): value <= 90 mmHg and decrease from baseline >= 20 mmHg, and value >= 160 mmHg and increase from baseline >= 20 mmHg.
Diastolic blood pressure (mmHg): value <= 50 mmHg and decrease from baseline >= 15 mmHg, and value >= 100 mmHg and increase from baseline >= 15 mmHg.
Pulse rate (beats per minute [bpm]): value <= 50 bpm and decrease from baseline >= 15 bpm, and value >= 120 bpm and increase from baseline >= 15 bpm.
Weight (kilograms [kg]): change >= 20 % decrease from baseline, and change >=10% increase from baseline.
Temperature (degree Celsius): value <=36 degree Celsius, and value >=37.5 degree Celsius.
Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
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Through end of the study
|
|
SLI: Number of Participants According to Categorization of Electrocardiogram (ECGs) Findings
時間枠：Through end of the study
|
ECG criteria included: ECG mean heart rate (beats per minute [bpm]): increase from baseline >25% and to a value >100 bpm; decrease from baseline >25% and to a value <50 bpm, PR interval not otherwise specified (milliseconds [msec]): new >280 msec, QRS interval not otherwise specified (msec): new >120 msec, QT Interval Corrected Using Fridericia's Formula (QTcF) not otherwise specified: new >450 msec; new >480 msec; new >500 msec; increase from baseline >30 msec and increase from baseline >60 msec.
Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
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Through end of the study
|
|
SLI: Number of Participants With Dose Modification of Any Study Intervention Due to AEs
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention.
Dose interruption: for encorafenib = 0 mg dose administered for >=1 days; for cetuximab, oxaliplatin, leucovorin, fluorouracil, irinotecan: >20 days between successive start dates with non-zero actual doses.
Dose reduction: decrease in dose of at least 10%, from the protocol-planned dose and a decrease from the previous non-zero dose; for encorafenib to qualify as a dose reduction, it should have lasted for >=2 days.
Dose modifications included both dose interruptions and reduction.
|
Through end of the study
|
|
SLI: Number of Participants With Dose Discontinuation of Any Study Intervention Due to AEs
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention.
Number of participants with dose discontinuation due to AEs were reported in this outcome measure.
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Through end of the study
|
|
SLI: ORR as Assessed by Investigator According to Line of Therapy - FAS
時間枠：From date of randomization until documented PD, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 33.9 months)
|
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.
|
From date of randomization until documented PD, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 33.9 months)
|
|
SLI: Duration of Response (DOR) as Assessed by Investigator According to Line of Therapy - FAS
時間枠：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)
|
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.
|
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)
|
|
SLI: PFS as Assessed by Investigator According to Line of Therapy - FAS
時間枠：From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 33.9 months)
|
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.
|
From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 33.9 months)
|
|
SLI: Time to Response (TTR) as Assessed by Investigator According to Line of Therapy - FAS
時間枠：From date of first dose to first radiographic evidence of response (CR or PR) (maximum up to 33.9 months [147.3 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 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.
|
From date of first dose to first radiographic evidence of response (CR or PR) (maximum up to 33.9 months [147.3 weeks])
|
|
SLI: Overall Survival (OS) According to Line of Therapy - FAS
時間枠：From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 33.9 months)
|
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.
|
From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 33.9 months)
|
|
SLI: Maximum Plasma Concentration (Cmax) of Encorafenib and Its Metabolite LHY746
時間枠：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
|
Cmax was observed directly from data.
LHY746 is a metabolite of Encorafenib.
|
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
|
|
SLI: Area Under the Concentration Time Profile From Time Zero to 6 Hours (AUC6) for Encorafenib and Its Metabolite LHY746
時間枠：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
|
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.
|
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
|
|
SLI: Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Encorafenib and Its Metabolite LHY746
時間枠：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
|
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.
|
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
|
|
SLI: Time to Maximum Plasma Concentration (Tmax) of Encorafenib and Its Metabolite LHY746
時間枠：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
|
Tmax: time (hours) to Cmax.
LHY746 is a metabolite of Encorafenib.
|
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
|
|
SLI: Apparent Total Clearance (CL/F) of Encorafenib
時間枠：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
|
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.
|
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
|
|
SLI, Cohort 1: Cmax of Irinotecan and Its Metabolite SN-38
時間枠：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
|
Cmax was observed directly from data.
SN-38 is a metabolite of Irinotecan.
|
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
|
|
SLI, Cohort 1: AUClast of Irinotecan and Its Metabolite SN-38
時間枠：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
|
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.
|
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
|
|
SLI, Cohort 1: Apparent Terminal Elimination Half-Life (t1/2) of Irinotecan and Its Metabolite SN-38
時間枠：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
|
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.
|
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
|
|
SLI, Cohort 1: CL/F of Irinotecan
時間枠：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
|
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.
|
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
|
|
SLI, Cohort 2: Cmax of Oxaliplatin
時間枠：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
|
Cmax was observed directly from data.
Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate.
|
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
|
|
SLI, Cohort 2: AUClast of Oxaliplatin
時間枠：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
|
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.
|
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
|
|
SLI, Cohort 2: CL/F of Oxaliplatin
時間枠：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
|
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.
|
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
|
|
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
時間枠：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
|
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".
|
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
|
|
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
時間枠：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
|
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".
|
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
|
|
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
時間枠：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
|
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".
|
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
|
|
SLI, Cohort 2: Ratio of AUClast on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Oxaliplatin
時間枠：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
|
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".
|
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
|
|
SLI, Cohort 2: Ratio of Cmax on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Oxaliplatin
時間枠：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
|
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".
|
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
|
|
Phase 3: OS for Arm B vs Arm C - FAS
時間枠：From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
|
OS was defined as the time from the date of first dose to death due to any cause.
If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact.
Analysis was performed using Kaplan Meier method.
|
From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: ORR by Derived Investigator Assessment for Arm B vs Arm C - FAS ORR Subset
時間枠：From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 24.71 months)
|
ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 by derived investigator assessment.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 24.71 months)
|
|
Phase 3: ORR as Assessed by BICR - FAS
時間枠：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)
|
ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 as assessed by BICR.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: DOR as Assessed by BICR for Arm B Versus Arm C - FAS ORR Subset
時間枠：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)
|
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 24.71 months)
|
|
Phase 3: DOR by Derived Investigator Assessment for Arm B Versus Arm C - FAS ORR Subset
時間枠：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)
|
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 24.71 months)
|
|
Phase 3: PFS as Assessed by BICR - FAS
時間枠：From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by BICR.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: OS - FAS
時間枠：From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
|
OS was defined as the time from the date of first dose to death due to any cause.
If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact.
Analysis was performed using Kaplan Meier method.
|
From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: PFS by Derived Investigator Assessment - FAS
時間枠：From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
|
PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause by derived investigator assessment.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of first dose to death due to any cause or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: TTR as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset
時間枠：From date of first dose to CR or PR (maximum up to 24.71 months [107.37 weeks])
|
TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by BICR.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
|
From date of first dose to CR or PR (maximum up to 24.71 months [107.37 weeks])
|
|
Phase 3: TTR by Derived Investigator Assessment for Arm B vs Arm C - FAS ORR Subset
時間枠：From date of first dose to CR or PR (maximum up to 24.71 months [107.37 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 24.71 months [107.37 weeks])
|
|
Phase 3: Progression After Next Line of Treatment (PFS2) - FAS
時間枠：From date of randomization to date of discontinuation of next-line treatment after PD or PD2 or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
PFS2 was defined as the time from the date of randomization to the date of discontinuation of next-line treatment after first objective PD by investigator assessment, to second objective disease progression (PD2), or death from any cause, whichever occurred first.
PD2: was progressive disease after the start of subsequent anticancer therapy based on investigator assessment.
PFS2 was censored at start date of next-line anticancer treatment (NTX) if PD date > NTX start date and there was no death, at last contact date if withdrawal of consent date >= date of randomization or end of study or if participant lost to follow-up or if no prior conditions are met or PD and no NTX and there was no death.
|
From date of randomization to date of discontinuation of next-line treatment after PD or PD2 or death or censoring date, whichever occurred first (maximum up to 37.25 months)
|
|
Phase 3: Number of Participants With AEs
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event.
AEs included both SAEs and all non-SAEs.
|
Through end of the study
|
|
Phase 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
AEs were graded according to NCI-CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
|
Through end of the study
|
|
Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
時間枠：Through end of the study
|
The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased.
Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death.
Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
時間枠：Through end of the study
|
The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and lipase increased.
Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
Only those chemistry parameters in which at least 1 participant in any of the reporting arm had any shift from grade <=2 at baseline to grade >=3 post-baseline are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: Number of Participants According to Categorization of Vital Signs Data
時間枠：Through end of the study
|
The criteria for vital signs included: Systolic blood pressure (mmHg): value <= 90 mmHg and decrease from baseline >= 20 mmHg, and value >= 160 mmHg and increase from baseline >= 20 mmHg.
Diastolic blood pressure (mmHg): value <= 50 mmHg and decrease from baseline >= 15 mmHg, and value >= 100 mmHg and increase from baseline >= 15 mmHg.
Pulse rate (bpm): value <= 50 bpm and decrease from baseline >= 15 bpm, and value >= 120 bpm and increase from baseline >= 15 bpm.
Weight (kg): change >= 20 % decrease from baseline, and change >=10% increase from baseline.
Temperature (degree Celsius): value <=36 degree Celsius, and value >=37.5 degree Celsius.
Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: Number of Participants According to Categorization of ECGs Findings
時間枠：Through end of the study
|
ECG criteria included: ECG mean heart rate (bpm): increase from baseline >25% and to a value >100 bpm; decrease from baseline >25% and to a value <50 bpm, PR interval not otherwise specified (msec): new >280 msec, QRS interval not otherwise specified (msec): new >120 msec, QTcF not otherwise specified: new >450 msec; new >480 msec; new >500 msec; increase from baseline >30 msec and increase from baseline >60 msec.
Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
|
Through end of the study
|
|
Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients - 30 Item Core Questionnaire (EORTC QLQC30) Global Health Status/Quality of Life Scores (QoL) at Baseline and Week 72
時間枠：Baseline and Week 72
|
EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures.
These included five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale.
Global health status/QoL scale ranged from 0 to 100; the higher score represents better level of functioning.
In this outcome measure, global health status/QoL scores are presented.
|
Baseline and Week 72
|
|
Phase 3: EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Visual Analogue Score (VAS) at Baseline and Week 72
時間枠：Baseline and Week 72
|
EQ-5D-5L is a standardized measure of health status.
The EQ-5D-5L consisted of EQ-5D-5L descriptive system and the EQ VAS.
For EQ VAS participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
|
Baseline and Week 72
|
|
Phase 3: Number of Participants According to Response to Patient Global Impression of Severity (PGIS) Assessment at Baseline and at Week 30
時間枠：Baseline and Week 30
|
PGIS is a single-item scale where participants rated the severity of colorectal cancer as follows: none, mild, moderate, severe and very severe.
|
Baseline and Week 30
|
|
Phase 3: Number of Participants According to Response to Patient Global Impression of Change (PGIC) Assessment at Week 30
時間枠：Week 30
|
The PGIC is a single-item scale where participants rated the overall change in colorectal cancer since participant started taking the study medication as follows: much better, a little better, no change, a little worse, and much worse.
|
Week 30
|
|
Phase 3: Trough Plasma Concentration of Encorafenib and Its Metabolite LHY746
時間枠：Predose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1
|
Trough plasma concentration of encorafenib and its metabolite LHY746 was measured in this outcome measure.
|
Predose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1
|
|
Phase 3: Cmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
時間枠：Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
Cmax was observed directly from data.
LHY746 is a metabolite of Encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: AUC6 of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
時間枠：Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5 and 6 hrs post-dose on Days 1 and 15 of Cycle 1
|
The AUC was estimated from time 0 to 6 hours post dose.
AUC6 was computed using the Linear/Log trapezoidal method.
LHY746 is a metabolite of Encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5 and 6 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: AUCtau of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
時間枠：Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval.
tau = 24 hrs for QD dosing of encorafenib.
LHY746 is a metabolite of encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: Tmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
時間枠：Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
Tmax: time (hours) to Cmax.
LHY746 is a metabolite of Encorafenib.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: CL/F of Encorafenib in Mainland China Participants
時間枠：Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf).
AUCinf was calculated as AUClast + (Clast*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 hrs post-dose on Days 1 and 15 of Cycle 1
|
|
Phase 3: Number of Participants Classified According to Microsatellite Instability (MSI) Status as Determined by Retrospective Central Testing of Baseline Tumor Tissue
時間枠：Baseline
|
MSI status was classified as follows; microsatellite instability-high (MSI-H): included participants with no negative test results and at least one positive test result, microsatellite stable (MSS): included participants with at least one negative test result and MSI-unknown: included participants with intermediate test results or not analyzed for MSI.
The number of participants as per their MSI status (MSI-H, MSS, and MSI-unknown) have been reported in this outcome measure.
|
Baseline
|
|
Phase 3: Number of Participants According to Circulating Tumor Deoxyribonucleic Acid (ctDNA) Status
時間枠：Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
ctDNA status was classified as follows; detected: overall variant allele frequency (VAF) was greater than zero, not detected: overall VAF equalled zero, and not evaluable: overall VAF could not be calculated.
The VAF was defined as percentage of deoxyribonucleic acid (DNA) reads at a specific position that show a genetic variant instead of the normal (reference) sequence.
The number of participants as per their ctDNA status (detected, not detected and not evaluable) have been reported in this outcome measure.
|
Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
|
Phase 3: Number of Participants According to B-Raf Serine/Threonine-Protein Kinase (BRAF) Valine 600 (V600) Status From ctDNA
時間枠：Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
BRAF V600 status from ctDNA was classified as follows; measurable: participants with detectable ctDNA had measurable BRAF V600 tumor biomarker alterations and not measurable: participants with detectable ctDNA did not have measurable BRAF V600 biomarker alterations or overall ctDNA was not detectable.
The number of participants as per their BRAF V600 status from ctDNA (measurable and not measurable) have been reported in this outcome measure.
In this outcome measure, data is presented for participants outside China and Mainland China participants.
|
Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (anytime till maximum of 37.25 months)
|
|
Cohort 3: PFS as Assessed by BICR - FAS
時間枠：From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first
|
PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by BICR.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first
|
|
Cohort 3: ORR by Derived Investigator Assessment - FAS
時間枠：From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 14.1 months)
|
ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 by derived investigator assessment.
CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
|
From date of randomization until documented PD, or start of subsequent anticancer therapy, or death, whichever occurred first (maximum up to 14.1 months)
|
|
Cohort 3: DOR as Assessed by BICR - FAS
時間枠：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
時間枠：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
時間枠：From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first
|
PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause by derived investigator assessment.
PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death >12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments.
Analysis was performed using Kaplan Meier method.
|
From date of randomization to earliest documentation of PD or death or censoring date, whichever occurred first
|
|
Cohort 3: OS - FAS
時間枠：From date of first dose to death due to any cause or censoring date, whichever occurred first
|
OS was defined as the time from the date of first dose to death due to any cause.
If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact.
Analysis was performed using Kaplan Meier method.
|
From date of first dose to death due to any cause or censoring date, whichever occurred first
|
|
Cohort 3: TTR as Assessed by BICR - FAS
時間枠：From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by BICR.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
|
From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
|
Cohort 3: TTR by Derived Investigator Assessment - FAS
時間枠：From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 by derived investigator assessment.
CR: disappearance of all target lesions and non-target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
|
From date of first dose to CR or PR (maximum up to 14.1 months [61.29 weeks])
|
|
Cohort 3: Number of Participants With AEs
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event.
AEs included both SAEs and all non-SAEs.
|
Through end of the study
|
|
Cohort 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
時間枠：Through end of the study
|
An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention.
AEs were graded according to NCI-CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE.
In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
|
Through end of the study
|
|
Cohort 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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.
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Through end of the study
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Cohort 3: Number of Participants According to Response to PGIS Assessment
時間枠：Through end of the study
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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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Through end of the study
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Cohort 3: Number of Participants According to Response to PGIC Assessment
時間枠：Through end of the study
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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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Through end of the study
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Cohort 3: Trough Plasma Concentration of Encorafenib and Its Metabolite LHY746
時間枠：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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Cohort 3: Number of Participants Classified According to MSI Status as Determined by Retrospective Central Testing
時間枠：Through end of the study
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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.
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Through end of the study
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Cohort 3: Number of Participants According to ctDNA Status
時間枠：Through end of the study
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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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Through end of the study
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Cohort 3: Number of Participants According to BRAF V600 Status From ctDNA
時間枠：Through end of the study
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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.
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Through end of the study
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Pfizer CT.gov Call Center、Pfizer
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2020年12月21日
一次修了 (実際)
2025年3月1日
研究の完了 (推定)
2027年12月28日
試験登録日
最初に提出
2020年10月5日
QC基準を満たした最初の提出物
2020年10月22日
最初の投稿 (実際)
2020年10月29日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月11日
QC基準を満たした最後の更新が送信されました
2026年5月15日
最終確認日
2026年5月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
- 部位別新生物
- 新生物
- 消化器疾患
- 消化器系疾患
- 結腸疾患
- 直腸腫瘍
- 結腸直腸腫瘍
- 結腸新生物
- 消化器腫瘍
- 腸の腫瘍
- 腸の病気
- 消化器系腫瘍
- 直腸疾患
- アミノ酸、ペプチド、およびタンパク質
- タンパク質
- 有機化学物質
- 複素環化化合物、1リング
- 複素環化化合物
- 複素環化化合物、2リング
- 複素環化化合物、融合リング
- 核酸、ヌクレオチド、およびヌクレオシド
- カムプトテシン
- アルカロイド
- 酵素と補酵素
- 抗体、モノクローナル、ヒト化
- 抗体、モノクローナル
- 抗体
- 免疫グロブリン
- 免疫タンパク質
- 血液タンパク質
- 血清グロブリン
- グロブリン
- 調整錯体
- デオキシシチジン
- シチジン
- ピリミジンヌクレオシド
- ピリミジン
- ヌクレオシド
- ホルミルテトラヒドロフォレート
- テトラヒドロフォレート
- 葉酸
- 羽毛
- プテリジン
- ウラシル
- ピリミジノン
- コエンザイム
- デオキシリボヌクレオシド
- カペシタビン
- オキサリプラチン
- ベバシズマブ
- イリノテカン
- セツキシマブ
- フルオロウラシル
- ロイコボリン
- レボルイコボリン
- Encorafenib
その他の研究ID番号
- C4221015
- BREAKWATER (その他の識別子：Pfizer)
- 2023-509405-77-00 (レジストリ識別子：CTIS (EU))
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
ファイザーは、匿名化された個々の参加者データおよび関連する研究文書へのアクセスを提供します (例:
プロトコル、統計分析計画 (SAP)、臨床研究報告書 (CSR)) は、有資格の研究者からの要求に応じて、特定の基準、条件、および例外に従います。
ファイザーのデータ共有基準とアクセス要求プロセスの詳細については、https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests をご覧ください。
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。