Clinical trial NCT02788279: A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)
Official title: A Phase III, Open-Label, Multicenter, Three-Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy vs. Regorafenib in Patients With Previously Treated Unresectable Locally Advanced or Metastatic Colorectal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Locally advanced or Metastatic colorectal adenocarcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-06-02
Enrollment: 363
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.


Eligibility criteria: Inclusion Criteria:

Disease-specific inclusion criteria:

* Histologically confirmed adenocarcinoma originating from the colon or rectum (Stage 4 American Joint Committee on Cancer \[AJCC\] 7th edition)
* 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

General inclusion criteria:

* 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:

* After the approximate 5% cap for microsatellite (MSI)-high participants is reached, only MSI-stable participants will be eligible
* 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization up to death due to any cause (up to approximately 20 months)
Secondary outcomes:
measure: Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: From randomization up to disease progression or death due to any cause (up to approximately 20 months)
measure: Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1
timeFrame: From randomization up to death due to any cause (up to approximately 20 months)
measure: Duration of Response (DOR) According to RECIST Version 1.1
timeFrame: From first occurrence of CR or PR up to disease progression or death due to any cause (up to approximately 20 months)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score
timeFrame: Baseline, end of the study (up to approximately 2.5 years)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study
timeFrame: Baseline, end of the study (up to approximately 2.5 years)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline, end of the study (up to approximately 2.5 years)
measure: Plasma Concentration of Cobimetinib
timeFrame: Predose (0 hours) and 3 to 6 hours after dose on Day 15 of Cycles 1 and 4 (1 cycle = 28 days) (up to approximately 2.5 years).
measure: Serum Concentration of Atezolizumab
timeFrame: Pre-infusion (0 hours) on Day 1 of Cycle 1 up to approximately 2.5 years. Detailed time frame is explained in the outcome measure description field.
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
timeFrame: Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4, 8, and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center; Medical Oncology
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists; SCRI
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists.
state: Florida
city: Harvey
country: United States
facility: Ingalls Cancer Research Center
state: Illinois
city: Edina
country: United States
facility: Southdale Cancer Clinic U of M Medical Center, Fairview- Edina
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: East Setauket
country: United States
facility: North Shore Hem Onc Associates
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: INTEGRIS Cancer Inst of OK
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute; Division of Medical Oncology
state: Pennsylvania
city: Chattanooga
country: United States
facility: SCRI Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Inst.
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital;North Coast Cancer Institute
state: New South Wales
city: St Leonards
country: Australia
facility: Northern Cancer Institute
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Adventist Hospital; Clinical Trial Unit
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre; Oncology
state: Victoria
city: Frankston
country: Australia
facility: Peninsula and South Eastern Haematology and Oncology Group
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health; Cancer Clinical Trial Centre
state: Victoria
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Charleroi
country: Belgium
facility: GHdC Site Notre Dame
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre-Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute; Clinical Trials
state: Alberta
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center, Cedar Cancer Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Québec
state: Quebec
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; Dept. of Clinical Oncology
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital; Clinical Oncology
city: Shatin
country: Hong Kong
facility: Prince of Wales Hosp; Dept. Of Clinical Onc
city: Napoli
country: Italy
facility: Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
state: Campania
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena; Oncologia
state: Emilia-Romagna
city: Genova
country: Italy
facility: Istit. Naz. per la Ricerca sul Cancro - Az. Osped. S. Martino
state: Liguria
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
state: Lombardia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
state: Puglia
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana; Oncologia
state: Toscana
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System/Severance Hospital
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o. o.
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
city: Lodz
country: Poland
facility: Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Dispensary
city: Moscow
country: Russian Federation
facility: N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
city: Omsk
country: Russian Federation
facility: BHI of Omsk region Clinical Oncology Dispensary
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Navarra
country: Spain
facility: Hospital de Navarra; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia; Servicio de Oncología
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital; Dept of Oncology
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham; Oncology Department
city: Manchester
country: United Kingdom
facility: The Christie; GI Research Office
city: Oxford
country: United Kingdom
facility: Churchill Hospital; Department of Oncology
city: Romford
country: United Kingdom
facility: Queen's Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital; Cancer Clinical Trials Centre
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital; Dept of Medical Oncology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.