A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma
coBRIM
A Phase III, Double-Blind, Placebo-Controlled Study of Vemurafenib Versus Vemurafenib Plus GDC-0973 in Previously Untreated BRAF^600-Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
2 other identifiers
interventional
495
18 countries
139
Brief Summary
To evaluate the efficacy of vemurafenib in combination with cobimetinib (GDC-0973), compared with vemurafenib and placebo, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma, as measured by progression-free survival (PFS), assessed by the study site investigator.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2013
Longer than P75 for phase_3
139 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 18, 2012
CompletedFirst Posted
Study publicly available on registry
September 21, 2012
CompletedStudy Start
First participant enrolled
January 8, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 9, 2014
CompletedResults Posted
Study results publicly available
October 30, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 21, 2019
CompletedMay 2, 2022
April 1, 2022
1.3 years
September 18, 2012
July 1, 2015
April 1, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival
Progression-free survival was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using Response Evaluation Criteria in Solid Tumors v1.1, or death from any cause, whichever came first. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)
Secondary Outcomes (3)
Overall Survival
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)
Percentage of Participants With an Objective Response
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)
Duration of Response
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)
Study Arms (2)
Placebo + Vemurafenib
ACTIVE COMPARATORParticipants will receive placebo orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 milligrams (mg) orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Cobimetinib + Vemurafenib
EXPERIMENTALParticipants will receive cobimetinib 60 mg orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Interventions
Vemurafenib supplied as tablets
Cobimetinib supplied as tablets
Eligibility Criteria
You may qualify if:
- Participants with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition. Unresectability of stage IIIc disease must have confirmation from a surgical oncologist
- Participants must be naïve to treatment for locally advanced unresectable or metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed
- Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test
- Measurable disease per RECIST v1.1
- Eastern Clinical Oncology Group performance status of 0 or 1
- Consent to provide archival for biomarker analyses
- Consent to undergo tumor biopsies for biomarker analyses
- Life expectancy greater than or equal to (≥) 12 weeks
- Adequate hematologic and end organ function
You may not qualify if:
- History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment
- Palliative radiotherapy within 14 days prior to the first dose of study treatment
- Major surgery or traumatic injury within 14 days prior to first dose of study treatment
- Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Participants with a previous malignancy within the past 3 years are excluded except for participants with resected basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast
- History of or evidence of retinal pathology on ophthalmological examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion, or neovascular macular degeneration
- Uncontrolled glaucoma with intraocular pressure
- Serum cholesterol ≥ Grade 2
- Hypertriglyceridemia ≥ Grade 2
- Hyperglycemia (fasting) ≥ Grade 2
- History of clinically significant cardiac dysfunction
- Participants with active central nervous system (CNS) lesions (including carcinomatous meningitis) are excluded. However, participants are eligible if:
- All known CNS lesions have been treated with stereotactic therapy or surgery, AND
- There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery
- Current severe, uncontrolled systemic disease
- History of malabsorption or other condition that would interfere with absorption of study drugs
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (156)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
The Angeles Clinic and Research Institute - W LA Office
Los Angeles, California, 90025, United States
University of California Davis Health System
Sacramento, California, 95817, United States
Sutter Pacific Medical Foundation
Santa Rosa, California, 95403, United States
University Of Colorado
Aurora, Colorado, 80045, United States
Florida Cancer Specialists - Broadway
Fort Myers, Florida, 33901, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33140, United States
Orlando Health Inc.
Orlando, Florida, 32806, United States
Northwestern Center For Clinical Research
Chicago, Illinois, 60611, United States
Uni of Kansas Medical Center; Dept of Neurology
Kansas City, Kansas, 66160-7314, United States
U of L - Physicians Pulmonology; Dept of Neuroradiology and Dept of Diagnostic Radiology
Louisville, Kentucky, 40202, United States
Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology
St Louis, Missouri, 63108, United States
Dartmouth-Hitchcock Medical Center; Department of Medicine
Lebanon, New Hampshire, 03756, United States
Novant Health Oncology Specialists
Winston-Salem, North Carolina, 27103, United States
University Hospitals of Cleveland
Cleveland, Ohio, 44106, United States
St. Luke's University Health network
Bethlehem, Pennsylvania, 18015, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261, United States
Rhode Island Hospital; Investigational Services
Providence, Rhode Island, 2903, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
Lake Macquarie Private Hospital
Gateshead, New South Wales, 2290, Australia
Lismore Base Hospital; Cancer Care & Haematology Unit
Lismore, New South Wales, 2480, Australia
Melanoma Institute Australia
North Sydney, New South Wales, 2060, Australia
Princess Alexandra Hospital
Woolloongabba, New South Wales, 2050, Australia
Royal Darwin Hospital
Casuarina, Northern Territory, 0811, Australia
Greenslopes Private Hospital
Greenslopes, Queensland, 4120, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029, Australia
Royal Adelaide Hospital; Hepatology
Adelaide, South Australia, 5000, Australia
Ashford Cancer Centre
Ashford SA, South Australia, 5035, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Launceston General Hospital; Gastroenterology Research
Launceston, Tasmania, 7250, Australia
Peninsula and South Eastern Haematology and Oncology Group
Frankston, Victoria, 3199, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, 3000, Australia
The Alfred Hospital
Prahan, Victoria, 3181, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, 6150, Australia
Ordensklinikum Linz Elisabethinen
Linz, 4020, Austria
Landesklinikum St. Pölten
Sankt Pölten, 3100, Austria
Medizinische Universität Wien
Vienna, 1090, Austria
Institut Jules Bordet; Department of Medical Oncology
Brussels, 1000, Belgium
Cliniques Universitaires St-Luc
Brussels, 1200, Belgium
UZ Antwerpen
Edegem, 2650, Belgium
Jessa Zkh (Campus Virga Jesse)
Hasselt, 3500, Belgium
CHU Sart-Tilman
Liège, 4000, Belgium
AZ Delta (Campus Rumbeke)
Roeselare, 8800, Belgium
BC Cancer Agency Vancouver Island Cancer Centre
Victoria, British Columbia, V8R 6V5, Canada
Juravinski Cancer Clinic; Department of Oncology
Hamilton, Ontario, L8V 5C2, Canada
The Ottawa Hospital Cancer Center; General Campus
Ottawa, Ontario, K1H 1C4, Canada
Toronto Sunnybrook Hospital
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Hospital; Department of Med Oncology
Toronto, Ontario, M5G 2M9, Canada
London Health Sciences Centre · Victoria Hospital;Department of Pediatrics
London, Quebec, N6A 4G5, Canada
McGill University Health Centre/Glen Site / Royal Victoria Hospital
Montreal, Quebec, H2W 1S6, Canada
Masarykuv onkologicky ustav
Brno, 656 53, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Fakultní nemocnice Olomouc
Olomouc, 775 20, Czechia
Fakultni nemocnice Ostrava
Ostrava - Poruba, 708 52, Czechia
Multiscan s.r.o.
Pardubice, 532 03, Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, 100 34, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 128 08, Czechia
Fakultni nemocnice Motol; Neurologicka klinika
Prague, 150 06, Czechia
Nemocnice Na Bulovce
Prague, 180 01, Czechia
Groupe Hospitalier Saint André - Hôpital Saint André
Bordeaux, 33075, France
Hôpital Ambroise Paré - Boulogne-Billancourt; Respiratory
Boulogne-Billancourt, 92104, France
CHU Clermont Ferrand - Hôpital d'Estaing
Clermont-Ferrand, 63003, France
CHU de Dijon - Hopital le Bocage
Dijon, 21000, France
Centre Hospitalier Universitaire de Grenoble - Albert Michallon
La Tronche, 38700, France
Hopital Claude Huriez - CHU Lille
Lille, 59037, France
Hopital de la Timone
Marseille, 13005, France
Hopital Saint Eloi
Montpellier, 34295, France
CHU NANTES - Hôtel Dieu; Pharmacy
Nantes, 44093, France
CHU Nice - Hopital de l'Archet 2
Nice, 06202, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495, France
Hopital Robert Debre; DERMATOLOGIE
Reims, 51092, France
Centre Eugene Marquis; Service d'oncologie
Rennes, 35042, France
St. Josef-Hospital; Studienambulanz
Bochum, 44791, Germany
Elbekliniken Buxtehude GmbH
Buxtehude, 21614, Germany
Universitaetsklinikum Koeln; Hematology/Oncology
Cologne, 50937, Germany
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
Dresden, 01307, Germany
Helios Klinikum Erfurt
Erfurt, 99089, Germany
Universitätsklinikum Essen
Essen, 45147, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
Gera, 07548, Germany
Universitätsmedizin Göttingen
Göttingen, 37075, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Kiel; Klinik fuer Allgemeine Innere Medizin
Kiel, 24105, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, 55101, Germany
Klinikum Mannheim GmbH Universitätsklinikum
Mannheim, 68167, Germany
Klinikum der Ludwigs-Maximilians-Universitaet Muenchen
München, 80337, Germany
Fachklinik Hornheide
Münster, 48157, Germany
Universitaetsklinikum Regensburg
Regensburg, 93053, Germany
Universitätsklinikum Tübingen
Tübingen, 72076, Germany
Universitätsklinikum Wurzburg
Würzburg, 97080, Germany
Orszagos Onkologiai Intezet
Budapest, 1122, Hungary
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
Gyula, 5700, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Pécs, 7624, Hungary
Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.
Szeged, 6720, Hungary
Soroka Medical Center; Oncology Dept
Beersheba, 8410100, Israel
Rambam Health Care Campus
Haifa, 3109600, Israel
HADASSAH UNIVERSITY HOSPITAL, EIN KAREM; Oncology
Jerusalem, 9112000, Israel
Rabin Medical Center-Beilinson Campus;Hematology-Oncology
Petah Tikva, 4941492, Israel
Chaim Sheba Medical Center
Ramat Gan, 5265601, Israel
Tel Aviv Sourasky MC, Dana children's hospital;Oncology Division
Tel Aviv, 6423906, Israel
Istituto Tumori Giovanni Paolo II IRCSS; Ospedale Oncologico Bari
Bari, Apulia, 70126, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, Campania, 80131, Italy
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
Meldola, Emilia-Romagna, 47014, Italy
A.O.U. Policlinico di Modena
Modena, Emilia-Romagna, 40124, Italy
Istituto Nazionale Tumori Regina Elena IRCCS
Rome, Lazio, 00144, Italy
Istituto Nazionale per la Ricerca sul Cancro di Genova
Genoa, Liguria, 16132, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
Bergamo, Lombardy, 24127, Italy
Asst Degli Spedali Civili Di Brescia
Brescia, Lombardy, 25100, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133, Italy
A.O.U. Senese Policlinico Santa Maria Alle Scotte
Siena, Tuscany, 53100, Italy
IOV - Istituto Oncologico Veneto IRCCS
Padua, Veneto, 35128, Italy
Amsterdam UMC Location VUMC
Amsterdam, 1081 HV, Netherlands
Leids Universitair Medisch Centrum; Cardiology
Leiden, 2333 ZA, Netherlands
Maastricht University Medical Center
Maastricht, 6229 HX, Netherlands
Auckland City Hospital
Auckland, 1023, New Zealand
Waikato Hospital
Hamilton, 3248, New Zealand
Radiumhospitalet
Oslo, 0379, Norway
TSBHI Altai Territorial oncological dispensary
Barnaul, 656045, Russia
FSBSI "N. N. Blokhin Russian Cancer Research Center"
Moscow, 115478, Russia
Moscow city oncology hospital #62 of Moscow Healthcare Department
Moscow, 143423, Russia
BHI of Omsk region Clinical Oncology Dispensary
Omsk, 644013, Russia
Pyatigorsky Oncologic Dispensary
Pyatigorsk, 357524, Russia
Complexo Hospitalario Universitario de Santiago
Santiago de Compostela, LA Coruña, 15706, Spain
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008, Spain
Hospital Universitario Virgen Macarena
Seville, Sevilla, 41071, Spain
Hospital Clínic i Provincial de Barcelona
Barcelona, 08036, Spain
MD Anderson Cancer Center
Madrid, 28033, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital General Universitario de Valencia
Valencia, 46014, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
Länssjukhuset Ryhov
Jönköping, 551 85, Sweden
Skånes Universitetssjukhus
Lund, 221 85, Sweden
Sahlgrenska Sjukhuset
Mölnlycke, 435 33, Sweden
Akademiska Sjukhuset
Uppsala, 751 85, Sweden
Inselspital-Universitaetsspital Bern
Bern, 3010, Switzerland
Kantonsspital Graubuenden
Chur, 7000, Switzerland
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, L7 8YA, United Kingdom
Barts and the London NHS Trust.
London, EC1A 7BE, United Kingdom
St George's Hospital; Courtyard Clinic
London, SW17 0QT, United Kingdom
Royal Marsden Hospital - Fulham
London, SW3 6JJ, United Kingdom
Royal Marsden Hospital - London
London, SW3 6JJ, United Kingdom
Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Nottingham University Hospitals; QMC Campus
Nottingham, NG7 2UH, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
Royal Cornwall Hospital
Truro, TR1 3LQ, United Kingdom
New Cross Hospital
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (7)
Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.
PMID: 36310331DERIVEDAscierto PA, Dreno B, Larkin J, Ribas A, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Atkinson V, Dutriaux C, Garbe C, Hsu J, Jones S, Li H, McKenna E, Voulgari A, McArthur GA. 5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation-Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study. Clin Cancer Res. 2021 Oct 1;27(19):5225-5235. doi: 10.1158/1078-0432.CCR-21-0809.
PMID: 34158360DERIVEDAscierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x.
PMID: 32746839DERIVEDde la Cruz-Merino L, Di Guardo L, Grob JJ, Venosa A, Larkin J, McArthur GA, Ribas A, Ascierto PA, Evans JTR, Gomez-Escobar A, Barteselli G, Eng S, Hsu JJ, Uyei A, Dreno B. Clinical features of serous retinopathy observed with cobimetinib in patients with BRAF-mutated melanoma treated in the randomized coBRIM study. J Transl Med. 2017 Jun 24;15(1):146. doi: 10.1186/s12967-017-1246-0.
PMID: 28646893DERIVEDDreno B, Ribas A, Larkin J, Ascierto PA, Hauschild A, Thomas L, Grob JJ, Koralek DO, Rooney I, Hsu JJ, McKenna EF, McArthur GA. Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study. Ann Oncol. 2017 May 1;28(5):1137-1144. doi: 10.1093/annonc/mdx040.
PMID: 28444112DERIVEDAscierto PA, McArthur GA, Dreno B, Atkinson V, Liszkay G, Di Giacomo AM, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Yan Y, Wongchenko M, Chang I, Hsu JJ, Koralek DO, Rooney I, Ribas A, Larkin J. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1248-60. doi: 10.1016/S1470-2045(16)30122-X. Epub 2016 Jul 30.
PMID: 27480103DERIVEDLarkin J, Ascierto PA, Dreno B, Atkinson V, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014 Nov 13;371(20):1867-76. doi: 10.1056/NEJMoa1408868. Epub 2014 Sep 29.
PMID: 25265494DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 18, 2012
First Posted
September 21, 2012
Study Start
January 8, 2013
Primary Completion
May 9, 2014
Study Completion
July 21, 2019
Last Updated
May 2, 2022
Results First Posted
October 30, 2015
Record last verified: 2022-04