A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)
NCT ID: NCT02788279
Last Updated: 2019-12-11
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
363 participants
INTERVENTIONAL
2016-07-05
2018-12-26
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Atezolizumab
Participants will receive atezolizumab monotherapy 1200 milligrams (mg) intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody
Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Cobimetinib + Atezolizumab
Participants will receive cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody
Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Cobimetinib
Participants will receive cobimetinib 60 mg orally on Days 1 to 21 in a 28-day cycle as a combination therapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Regorafenib
Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Regorafenib
Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Interventions
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Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody
Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Cobimetinib
Participants will receive cobimetinib 60 mg orally on Days 1 to 21 in a 28-day cycle as a combination therapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Regorafenib
Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Eligibility Criteria
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Inclusion Criteria
* Experienced disease progression or was intolerant to at least two systemic chemotherapy regimens for metastatic colorectal cancer that must have included fluroropyrimidines, irinotecan, and oxaliplatin; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion; disease progression must have occurred within 3 months of the last systemic therapy administration
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Anticipated life expectancy greater than or equal to (\>=) 3 months
* Adequate hematologic and end organ function
* Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of less than \[\<\] 1 percent \[%\] per year) during the treatment period, within 5 months after the last dose of atezolizumab, and within 3 months after the last dose of cobimetinib and regorafenib
* Men must agree not to donate sperm or have intercourse with a female partner without using appropriate barrier contraception during the treatment period and for 3 months after the last dose of either cobimetinib or regorafenib
* Provide an archival or newly obtained tumor tissue sample
Exclusion Criteria
* Once the 50% cap for wild-type RAS has been reached, only extended RAS-mutant participants will be eligible
* Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment
* Treatment with any anti-cancer agent within 14 days prior to Cycle 1 Day 1
* Uncontrolled tumor-related pain. Participants requiring narcotic pain medication must be on a stable regimen at study entry
* Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed
* Active or untreated central nervous system (CNS) metastases are excluded
* Prior therapy with any cancer immunotherapy, MEK inhibitor, or regorafenib
* Participants with active malignancy (other than CRC) or a prior malignancy within the past 3 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
* Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure New York Heart Association Class II or higher
* Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or below 50%, whichever is lower
* Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 millimeters of Mercury (mmHg) despite optimal medical management
* Human immunodeficiency virus (HIV) infection
* Active tuberculosis infection
* Severe infections within 2 weeks prior to Cycle 1 Day 1
* Active or chronic viral hepatitis B or C infection
* History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion, or neovascular macular degeneration
* Participants will be excluded if they currently have any of the risk factors as defined in the study protocol for retinal vein occlusion
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
* History of organ transplantation including allogeneic bone marrow transplantation
* Inability to swallow medications
* Malabsorption condition that would alter the absorption of orally administered medications
* Pregnant, lactating, breastfeeding, or intending to become pregnant during the study
* Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation of a live attenuated vaccine will be required during the study
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
Yale Cancer Center; Medical Oncology
New Haven, Connecticut, United States
Georgetown University
Washington D.C., District of Columbia, United States
Florida Cancer Specialists; SCRI
Fort Myers, Florida, United States
Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
Jacksonville, Florida, United States
Florida Cancer Specialists.
St. Petersburg, Florida, United States
Ingalls Cancer Research Center
Harvey, Illinois, United States
Southdale Cancer Clinic U of M Medical Center, Fairview- Edina
Edina, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
North Shore Hem Onc Associates
East Setauket, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
INTEGRIS Cancer Inst of OK
Oklahoma City, Oklahoma, United States
University of Pittsburgh Cancer Institute; Division of Medical Oncology
Pittsburgh, Pennsylvania, United States
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, United States
Sarah Cannon Research Inst.
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
Medical Oncology Associates
Spokane, Washington, United States
Port Macquarie Base Hospital;North Coast Cancer Institute
Port Macquarie, New South Wales, Australia
Northern Cancer Institute
St Leonards, New South Wales, Australia
Sydney Adventist Hospital; Clinical Trial Unit
Sydney, New South Wales, Australia
Monash Medical Centre; Oncology
Clayton, Victoria, Australia
Peninsula and South Eastern Haematology and Oncology Group
Frankston, Victoria, Australia
Austin Health; Cancer Clinical Trial Centre
Heidelberg, Victoria, Australia
Imeldaziekenhuis
Bonheiden, , Belgium
Cliniques Universitaires St-Luc
Brussels, , Belgium
GHdC Site Notre Dame
Charleroi, , Belgium
AZ Groeninge
Kortrijk, , Belgium
UZ Leuven Gasthuisberg
Leuven, , Belgium
Tom Baker Cancer Centre-Calgary
Calgary, Alberta, Canada
Cross Cancer Institute; Clinical Trials
Edmonton, Alberta, Canada
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
The Ottawa Hospital
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
McGill University Health Center, Cedar Cancer Center
Montreal, Quebec, Canada
Hopital du Sacre-Coeur
Montreal, Quebec, Canada
CHU de Québec
Québec, Quebec, Canada
Queen Mary Hospital; Dept. of Clinical Oncology
Hong Kong, , Hong Kong
Tuen Mun Hospital; Clinical Oncology
Hong Kong, , Hong Kong
Prince of Wales Hosp; Dept. Of Clinical Onc
Shatin, , Hong Kong
IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
San Giovanni Rotondo, Apulia, Italy
Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
Napoli, Campania, Italy
A.O. Universitaria Policlinico Di Modena; Oncologia
Modena, Emilia-Romagna, Italy
Istit. Naz. per la Ricerca sul Cancro - Az. Osped. S. Martino
Genoa, Liguria, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
Milan, Lombardy, Italy
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Milan, Lombardy, Italy
A.O. Universitaria Pisana; Oncologia
Pisa, Tuscany, Italy
Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy
Bydgoszcz, , Poland
Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
Gdansk, , Poland
Szpitale Pomorskie Sp. z o. o.
Gdynia, , Poland
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
Krakow, , Poland
Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii
Lodz, , Poland
Arkhangelsk Regional Clinical Oncology Dispensary
Arkhangelsk, , Russia
N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
Moscow, , Russia
BHI of Omsk region Clinical Oncology Dispensary
Omsk, , Russia
National Cancer Center
Gyeonggi-do, , South Korea
Chonnam National University Hwasun Hospital
Jeollanam-do, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Asan Medical Center - Oncology
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Yonsei University Health System/Severance Hospital
Seoul, , South Korea
Hospital de Navarra; Servicio de Oncologia
Navarra, Navarre, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, , Spain
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, , Spain
Hospital Clinico San Carlos; Servicio de Oncologia
Madrid, , Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid, , Spain
Hospital Clínico Universitario de Valencia; Servicio de Oncología
Valencia, , Spain
Birmingham Heartlands Hospital; Dept of Oncology
Birmingham, , United Kingdom
Royal Marsden Hospital - Fulham; Oncology Department
London, , United Kingdom
The Christie; GI Research Office
Manchester, , United Kingdom
Churchill Hospital; Department of Oncology
Oxford, , United Kingdom
Queen's Hospital
Romford, , United Kingdom
Weston Park Hospital; Cancer Clinical Trials Centre
Sheffield, , United Kingdom
Royal Marsden Hospital; Dept of Medical Oncology
Sutton, , United Kingdom
Countries
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References
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Taraborrelli L, Senbabaoglu Y, Wang L, Lim J, Blake K, Kljavin N, Gierke S, Scherl A, Ziai J, McNamara E, Owyong M, Rao S, Calviello AK, Oreper D, Jhunjhunwala S, Argiles G, Bendell J, Kim TW, Ciardiello F, Wongchenko MJ, de Sauvage FJ, de Sousa E Melo F, Yan Y, West NR, Murthy A. Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer. Nat Commun. 2023 Sep 23;14(1):5945. doi: 10.1038/s41467-023-41618-7.
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.
Eng C, Kim TW, Bendell J, Argiles G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F; IMblaze370 Investigators. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2019 Jun;20(6):849-861. doi: 10.1016/S1470-2045(19)30027-0. Epub 2019 Apr 16.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2016-000202-11
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GO30182
Identifier Type: -
Identifier Source: org_study_id