A Study of Biomarker-Driven Therapy in Metastatic Colorec... | NCT02291289 | Trialant
NCT02291289
Sponsor
Hoffmann-La Roche
Status
Completed
Last Update Posted
May 6, 2024Actual
Enrollment
1,044Actual
Phase
Phase 2
Conditions
Colorectal Cancer
Interventions
Cetuximab
FOLFOX induction regimen
Fluoropyrimidine (5-FU/LV or capecitabine)
Atezolizumab
Vemurafenib
Bevacizumab
Trastuzumab
Pertuzumab
Cobimetinib
5-FU/LV
Capecitabine
Countries
Argentina
Belgium
Bosnia and Herzegovina
Brazil
Denmark
Egypt
France
Germany
Greece
Italy
Mexico
Netherlands
Poland
Portugal
Russia
Serbia
Slovakia
Slovenia
South Korea
Spain
Sweden
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02291289
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MO29112
Secondary IDs
ID
Type
Description
Link
2014-001017-61
EudraCT Number
Brief Title
A Study of Biomarker-Driven Therapy in Metastatic Colorectal Cancer (mCRC)
Official Title
A Multi-Centre Randomised Clinical Trial of Biomarker-Driven Maintenance Treatment for First-Line Metastatic Colorectal Cancer (MODUL)
Acronym
MODUL
Organization
Hoffmann-La RocheINDUSTRY
Status Module
Record Verification Date
Oct 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Apr 17, 2015Actual
Primary Completion Date
May 31, 2019Actual
Completion Date
Mar 24, 2021Actual
First Submitted Date
Nov 11, 2014
First Submission Date that Met QC Criteria
Nov 11, 2014
First Posted Date
Nov 14, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
May 28, 2020
Results First Submitted that Met QC Criteria
Jul 8, 2020
Results First Posted Date
Jul 24, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Nov 1, 2023
Last Update Posted Date
May 6, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Hoffmann-La RocheINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This randomized, multi-center, active-controlled, open-label, parallel-group study will investigate the efficacy and safety of biomarker-driven maintenance treatment for first-line mCRC. Participants with mCRC are eligible for entry and cannot have received any prior chemotherapy in the metastatic setting. The entire study duration is anticipated to be approximately 7.5 years.
Detailed Description
Not provided
Conditions Module
Conditions
Colorectal Cancer
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
1,044Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1: Induction Phase (IP)
Other
Includes participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Drug: FOLFOX induction regimen
Drug: Bevacizumab
Drug: 5-FU/LV
Cohort 2 (IP)
Other
Includes participants with BRAFwt. All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Drug: FOLFOX induction regimen
Drug: Bevacizumab
Drug: 5-FU/LV
Cohort 3 (IP)
Other
Includes participants with human epidermal growth factor receptor 2 positive (HER2+). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Drug: FOLFOX induction regimen
Drug: Bevacizumab
Drug: 5-FU/LV
Cohort 4 (IP)
Other
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Cetuximab
Drug
500 mg/m^2 via IV infusion on Day 1 of every 2-week cycle
PFS is defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
From randomization until disease progression or death from any cause, up to 5 years
Secondary Outcomes
Measure
Description
Time Frame
Overall Survival (OS)
OS is defined as the time from randomization into the MTP to time of death from any cause.
From randomization until death from any cause, up to 5 years
Percentage of Participants With Adverse Events
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
ECOG PS of less than or equal to (<=) 2
At least 16 weeks of life expectancy at time of entry into the study
Histologically confirmed colorectal cancer (CRC) with mCRC confirmed radiologically
Measureable, unresectable disease according to RECIST 1.1
No prior chemotherapy for CRC in the metastatic setting
Archival tumor formalin-fixed paraffin-embedded tissue block from the primary tumor obtained at the time of the initial diagnosis is available
Adequate hematological, liver and renal function
Agreement to use highly effective measures of contraception
Exclusion Criteria for All Participants:
Less than 6 months from completion of any prior neoadjuvant or adjuvant chemotherapy, radiotherapy
Prior or current treatment with bevacizumab or any other anti-angiogenic drug (vascular endothelial growth factor or vascular endothelial growth factor receptor therapies or tyrosine kinase inhibitors)
Current or recent (within 10 days of study enrollment) use of aspirin (more than [>] 325 milligrams per day [mg/day]), clopidogrel (> 75 mg/day), or current or recent (within 10 days prior to the start of study induction treatment) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic uses allowed)
Active infection requiring intravenous antibiotics at the start of study induction treatment
Previous or concurrent malignancy, except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the participant has been disease-free for 5 years prior to study entry
Inadequately controlled hypertension; prior history of hypertensive crisis or hypertensive encephalopathy
Clinically significant (active) cardiovascular disease, for example cerebrovascular accidents <= 6 months prior to start of study induction treatment, myocardial infarction <= 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Functional Classification Grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study induction treatment
Active symptomatic or untreated central nervous system (CNS) metastases; CNS disease other than supratentorial or cerebellar metastases (in other words, patients with metastases to midbrain, pons, medulla or spinal cord are excluded); history of or known carcinomatous meningitis
Known hypersensitivity to any component of any of the study induction or maintenance treatment medications
Pregnancy or lactation
Exclusion Criteria for Participants in Cohort 1 (MP):
Inability to swallow pills
Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption
History or presence of clinically significant ventricular or atrial dysrhythmias
Corrected QT (QTc) interval >= 450 millisecond assessed within 3 weeks prior to randomization, long QT syndrome or, uncorrectable electrolyte abnormalities (including magnesium) or requirement for medicinal products known to prolong the QT interval
ECOG PS > 2
Exclusion Criteria for Participants in Cohort 2 (MP):
Prior allogeneic bone marrow transplantation or prior solid organ transplantation
History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis at most recent chest imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI])
Positive test for human immunodeficiency virus (HIV)
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) at Screening
Active tuberculosis
Severe infection within 4 weeks prior to start of maintenance treatment including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia; has signs or symptoms of significant infection or has received oral or IV antibiotics within 2 weeks prior to start of maintenance treatment
Administration of a live, attenuated vaccine within 4 weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study
Prior treatment with cluster of differentiation (CD) 137 agonists, anti-cytotoxic T-lymphocyte-associated antigen (CTLA) 4, anti-programmed death-1 (PD-1), or anti-programmed death-ligand 1 (PD-L1) therapeutic antibody or pathway-targeting agents
Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of maintenance treatment
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of maintenance treatment, or anticipated requirement for systemic immunosuppressive medications during the remainder of the study
If receiving receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (for example, denosumab) and unwilling to adopt alternative treatment such as bisphosphonates while receiving atezolizumab
Exclusion Criteria for Participants in Cohort 3 (MP):
Inability to swallow pills
Left ventricular ejection fraction (LVEF) less than (<) 50 percent (%) as assessed after completion of induction treatment by either 2-dimensional echocardiogram or multiple-gated acquisition
Clinically significant cardiovascular disease, including unstable angina, history of or active congestive heart failure of ≥ NYHA Grade 2, history of or ongoing serious cardiac arrhythmia requiring treatment (except for controlled atrial fibrillation and/or paroxysmal supraventricular tachycardia).
Current uncontrolled hypertension with or without medication
Current dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy
Insulin-dependent diabetes
Current known infection with HIV, HBV, or HCV (active infection or carriers)
Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine
Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
Known hypersensitivity to murine proteins
Exclusion Criteria for Participants in Cohort 4 (MP):
History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on most recent chest imaging (CT scan or MRI)
Malabsorption condition that would alter the absorption of orally administered medications
Amylase or lipase ≥ 1.5 times the upper limit of normal within 14 days prior to maintenance treatment initiation
Serum albumin less than (<) 2.5 grams per deciliter (g/dL)
LVEF < institutional lower limit of normal or < 50%, whichever is lower
Poorly controlled hypertension
Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters are allowed
Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure ≥ NYHA Grade 2
History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of maintenance treatment
History or evidence of intracranial hemorrhage or spinal cord hemorrhage
Evidence of clinically significant vasogenic edema
Any hemorrhage or bleeding event ≥ National Cancer Institute Common Terminology Criteria for Adverse Events Grade 3 within 28 days prior to initiation of maintenance treatment
History 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
Positive HIV test
Active HBV or HCV
Active tuberculosis
Severe infection within 4 weeks prior to start of maintenance treatment including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia; has signs or symptoms of significant infection or has received oral or IV antibiotics within 2 weeks prior to start of maintenance treatment.
Prior allogeneic bone marrow transplantation or prior solid organ transplantation
Administration of a live, attenuated vaccine within 4 weeks prior to start of study maintenance treatment or anticipation that such a live attenuated vaccine will be required during the study
Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
Prior treatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) or ERK inhibitor
Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of study maintenance treatment
Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to start of study maintenance treatment, or requirement for systemic immunosuppressive medications during the trial.
If receiving a RANKL inhibitor (for example, denosumab), unwilling to adopt alternative treatment such as (but not limited to) bisphosphonates, while receiving atezolizumab.
Consumption of foods, supplements or drugs that are potent cytochrome P450 3A4 (CYP3A4) enzyme inducers or inhibitors ≤ 7 days before initiation of study maintenance treatment or expected concomitant use during maintenance treatment. These include St. John's wort or hyperforin (potent CYP3A4 enzyme inducer) and grapefruit juice (potent CYP3A4 enzyme inhibitor)
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Clinical Trials
Hoffmann-La Roche
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de OncologÃa
Ducreux M, Tabernero J, Grothey A, Arnold D, O'Dwyer PJ, Gilberg F, Abbas A, Thakur MD, Prizant H, Irahara N, Tahiri A, Schmoll HJ, Van Cutsem E, de Gramont A. Clinical and exploratory biomarker findings from the MODUL trial (Cohorts 1, 3 and 4) of biomarker-driven maintenance therapy for metastatic colorectal cancer. Eur J Cancer. 2023 May;184:137-150. doi: 10.1016/j.ejca.2023.01.023. Epub 2023 Feb 4.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Participants initially received study treatment during the Induction Phase. Next, participants within each cohort based on biomarker status were randomized to either an experimental arm or control arm per cohort in the Maintenance Phase. BRAFmut participants experiencing early disease progression during induction treatment had the option of proceeding immediately to receive second-line treatment and were followed during the study, but were not part of the Maintenance Phase study objectives.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort 1: Induction Phase (IP)
Included participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
Periods
Title
Milestones
Reasons Not Completed
Induction Treatment
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Feb 18, 2020
May 28, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Algeria
Cyprus
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Includes participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) will receive 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
Drug: Cetuximab
Drug: Vemurafenib
Drug: 5-FU/LV
Cohort 1 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Active Comparator
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Drug: Fluoropyrimidine (5-FU/LV or capecitabine)
Drug: Bevacizumab
Cohort 2 (MP):5-FU/LV or capecitabine,bevacizumab,atezolizumab
Experimental
Participants with BRAFwt will receive fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
Drug: Fluoropyrimidine (5-FU/LV or capecitabine)
Drug: Atezolizumab
Drug: Bevacizumab
Cohort 2 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Active Comparator
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) will receive 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
Drug: Trastuzumab
Drug: Pertuzumab
Drug: Capecitabine
Cohort 3 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Active Comparator
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Drug: Fluoropyrimidine (5-FU/LV or capecitabine)
Drug: Bevacizumab
Cohort 4 (MP): Cobimetinib,atezolizumab
Experimental
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) will receive 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
Drug: Atezolizumab
Drug: Cobimetinib
Cohort 4 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Active Comparator
Per Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Drug: Fluoropyrimidine (5-FU/LV or capecitabine)
Drug: Bevacizumab
Early Progressing BRAFmut Cohort
Other
BRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
Drug: Cetuximab
Drug: Fluoropyrimidine (5-FU/LV or capecitabine)
Drug: Atezolizumab
Drug: Vemurafenib
Drug: Bevacizumab
Drug: 5-FU/LV
FOLFOX induction regimen
Drug
Administered per the Investigator's discretion in accordance with locally approved prescribing information.
Cohort 1: Induction Phase (IP)
Cohort 2 (IP)
Cohort 3 (IP)
Cohort 4 (IP)
Fluoropyrimidine (5-FU/LV or capecitabine)
Drug
Per Investigator's discretion: 5-FU 1600-2400 mg/m^2 administered via 46-hour IV infusion on Day 1 of every 2-week cycle and LV 400 mg/m^2 administered via a 2-hour infusion on Day 1 every 2 weeks or 1000 mg/m^2 twice-daily capecitabine (BID) by mouth given days 1-14 every 2 weeks. The chosen fluoropyrimidine should be administered in accordance with local prescribing information.
Cohort 1 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Cohort 2 (MP):5-FU/LV or capecitabine,bevacizumab,atezolizumab
Cohort 2 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Cohort 3 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Cohort 4 Control (MP): 5-FU/LV or capecitabin, bevacizumab
Early Progressing BRAFmut Cohort
Atezolizumab
Drug
800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle, or a fixed dose of 840 mg
Cohort 2 (MP):5-FU/LV or capecitabine,bevacizumab,atezolizumab
60 mg orally once daily for 3 weeks followed by a 1-week treatment break
Cohort 4 (MP): Cobimetinib,atezolizumab
RO5514041
5-FU/LV
Drug
1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle until disease progression per the Investigator's assessment using modified Response Evaluation Criteria in Solid Tumors or death from any cause, whichever occurs first. The fluoropyrimidine should be administered in accordance with local prescribing information.
1000 mg/m^2 twice-daily capecitabine (BID) by mouth given days 1-14 every 2 weeks. The fluoropyrimidine should be administered in accordance with local prescribing information.
Calculated as the number of participants with a best overall response of CR or PR according to RECIST 1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR= CR + PR.
From randomization until disease progression, up to 5 years
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
From randomization until disease progression, up to 5 years
Time to Treatment Response
Calculated as the time from randomization to the first Occurrence of a documented Objective Response (CR or PR) determined according to RECIST 1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
From randomization until disease progression or death from any cause, up to 5 years
Duration of Response
Defined as the time from the first assessment of CR or PR until disease progression or death from any cause, whichever occurs first. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
From first objective response until disease progression or death from any cause, up to 5 years
Percentage of Participants With Improvement and/or Stayed the Same on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
FG002
Cohort 1 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
FG003
Cohort 2 (IP)
Included participants with BRAFwt. All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
FG004
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
FG005
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
FG006
Cohort 3 (IP)
Included participants with human epidermal growth factor receptor 2 positive (HER2+). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
FG008
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
FG009
Cohort 4 (IP)
Included participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
FG010
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
FG011
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
FG012
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment had the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor was MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor was MSI-H. This cohort was followed during the study, but was not part of the Maintenance Phase study objectives.
FG00093 subjects
FG0010 subjects
FG0020 subjects
FG003635 subjects
FG0040 subjects
FG0050 subjects
FG0066 subjects
FG0070 subjects
FG0080 subjects
FG009310 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Treated During Induction Phase
FG00093 subjects
FG0010 subjects
FG0020 subjects
FG003632 subjects
FG0040 subjects
FG0050 subjects
FG0066 subjects
FG0070 subjects
FG0080 subjects
FG009309 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
COMPLETED
FG00063 subjects
FG0010 subjects
FG0020 subjects
FG003460 subjects
FG0040 subjects
FG0050 subjects
FG0065 subjects
FG0070 subjects
FG0080 subjects
FG009135 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
NOT COMPLETED
FG00030 subjects
FG0010 subjects
FG0020 subjects
FG003175 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG009175 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00324 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG00918 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG004
Death
FG00025 subjects
FG0010 subjects
FG0020 subjects
FG003111 subjects
FG004
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG00312 subjects
FG004
Non-Compliance
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Reason Not Specified
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0034 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG004
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG004
Missing
FG0004 subjects
FG0010 subjects
FG0020 subjects
FG00314 subjects
FG004
Maintenance Treatment Phase
Type
Comment
Milestone Data
STARTED
FG0000 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG00140 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG00220 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG0030 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG004297 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG005148 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG0060 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG0073 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG0082 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG0090 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG01065 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG01134 subjectsParticipants from IP Cohorts were randomized to the MP Cohorts based on bio-marker assessments.
FG0120 subjects
Treated During Maintenance Phase
FG0000 subjects
FG00140 subjects
FG00218 subjects
FG0030 subjects
FG004
COMPLETED
FG0000 subjects
FG0016 subjects
FG0022 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG00134 subjects
FG00218 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Early Disease Progression
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG01211 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1: Induction Phase (IP)
Included participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
BG001
Cohort 2 (IP)
Included participants with BRAFwt. All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
BG002
Cohort 3 (IP)
Included participants with human epidermal growth factor receptor 2 positive (HER2+). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
BG003
Cohort 4 (IP)
Included participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00093
BG001635
BG0026
BG003310
BG0041044
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00059.5± 12.0
BG00160.9± 12.6
BG00248.0± 7.7
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
In utero
BG0000
BG0010
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00049
BG001247
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0005
BG00152
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0001
BG0019
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
Participants that were in the Maintenance Phase of the study, which included the experimental and control arms of Cohorts 1-4.
Posted
Median
95% Confidence Interval
months
From randomization until disease progression or death from any cause, up to 5 years
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
OG001
Cohort 1 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG002
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG003
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG005
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG007
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Units
Counts
Participants
OG00040
OG00120
OG002297
OG003
Title
Denominators
Categories
Title
Measurements
OG0009.99(7.72 to 12.55)
OG00111.60(3.58 to 15.67)
OG0027.13(6.14 to 8.41)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
= 0.872
Hazard Ratio (HR)
0.95
2-Sided
95
0.50
1.82
Superiority
OG002
OG003
Log Rank
= 0.666
Secondary
Overall Survival (OS)
OS is defined as the time from randomization into the MTP to time of death from any cause.
Participants that were in the Maintenance Phase of the study, which included the experimental and control arms of Cohorts 1-4.
Posted
Median
95% Confidence Interval
months
From randomization until death from any cause, up to 5 years
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
OG001
Cohort 1 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG002
Secondary
Percentage of Participants With Adverse Events
Safety population: all participants who received an intervention during the study.
Posted
Number
percentage of participants
From baseline until end of study (up to 5 years)
ID
Title
Description
OG000
Cohort 1: Induction Phase (IP)
Included participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
Secondary
Overall Response
Calculated as the number of participants with a best overall response of CR or PR according to RECIST 1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR= CR + PR.
Participants that were in the Maintenance Phase of the study, which included the experimental and control arms of Cohorts 1-4.
Posted
Count of Participants
Participants
From randomization until disease progression, up to 5 years
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
OG001
Cohort 1 Control(MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Secondary
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
Participants that were in the Maintenance Phase of the study, which included the experimental and control arms of Cohorts 1-4.
Posted
Count of Participants
Participants
From randomization until disease progression, up to 5 years
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
OG001
Secondary
Time to Treatment Response
Calculated as the time from randomization to the first Occurrence of a documented Objective Response (CR or PR) determined according to RECIST 1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Participants that were in the Maintenance Phase of the study, which included the experimental and control arms of Cohorts 1-4.
Posted
Median
Full Range
months
From randomization until disease progression or death from any cause, up to 5 years
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
OG001
Cohort 1 Control(MP):5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Secondary
Duration of Response
Defined as the time from the first assessment of CR or PR until disease progression or death from any cause, whichever occurs first. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Participants that were in the Maintenance Phase of the study, which included the experimental and control arms of Cohorts 1-4.
Posted
Median
95% Confidence Interval
months
From first objective response until disease progression or death from any cause, up to 5 years
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
OG001
Cohort 1 Control(MP):5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Secondary
Percentage of Participants With Improvement and/or Stayed the Same on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
Participants that were in the Maintenance Phase of the study, which included the experimental and control arms of Cohorts 1-4.
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
OG001
Cohort 1 Control(MP):5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG002
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Time Frame
From baseline until end of study (up to 5 years)
Description
All-cause mortality was based on the intent-to-treat (ITT) population, which included all participants randomized in the study. Serious Adverse Events and Other Adverse Events were based on the safety population, which included all participants who received an intervention during the study.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1: Induction Phase (IP)
Included participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
Participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) received 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
29
40
15
40
40
40
EG002
Cohort 1 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
16
20
5
18
17
18
EG003
Cohort 2 (IP)
Included participants with BRAFwt. All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
111
635
232
632
608
632
EG004
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
188
297
76
293
270
293
EG005
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
107
148
20
143
120
143
EG006
Cohort 3 (IP)
Included participants with human epidermal growth factor receptor 2 positive (HER2+). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
1
3
0
3
3
3
EG008
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
1
2
0
2
2
2
EG009
Cohort 4 (IP)
Included participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
82
310
93
309
298
309
EG010
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
46
65
26
64
61
64
EG011
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
19
34
3
34
29
34
EG012
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment had the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor was MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor was MSI-H. This cohort was followed during the study, but was not part of the Maintenance Phase study objectives.
10
11
3
11
11
11
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG0031 events1 affected632 at risk
EG0040 events0 affected293 at risk
EG0050 events0 affected143 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected3 at risk
EG0080 events0 affected2 at risk
EG0091 events1 affected309 at risk
EG0100 events0 affected64 at risk
EG0110 events0 affected34 at risk
EG0120 events0 affected11 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Acute coronary syndrome
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cardiogenic shock
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Coronary artery disease
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Restrictive cardiomyopathy
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Supraventricular tachycardia
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Chorioretinopathy
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0005 events5 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Faecaloma
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Immune-mediated enterocolitis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Intestinal perforation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Large intestinal stenosis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Large intestine perforation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Lower gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Proctalgia
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Subileus
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0004 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Asthenia
General disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Chest pain
General disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gait disturbance
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
General physical health deterioration
General disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Implant site thrombosis
General disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Infusion site extravasation
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pyrexia
General disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cholestasis
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hepatocellular injury
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hepatorenal failure
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hepatotoxicity
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal wall abscess
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Anal abscess
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Arthritis infective
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Device related infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Erysipelas
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gingivitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hepatic infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Large intestine infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Post procedural sepsis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rectal abscess
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Sepsis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Septic shock
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Urosepsis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Vascular device infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Anastomotic ulcer
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Incisional hernia
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pelvic fracture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Post procedural haemorrhage
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Spinal fracture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Tracheal haemorrhage
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blood triglycerides increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Lipase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0005 events3 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Leiomyosarcoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Second primary malignancy
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Tumour perforation
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Syncope
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Acute respiratory distress syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0002 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Organising pneumonia
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Arterial thrombosis
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypertension
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypotension
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Superior vena cava syndrome
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Thrombosis
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrointestinal obstruction
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Large intestinal obstruction
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Fatigue
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hyperthermia
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Implant site dehiscence
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Anaphylactic reaction
Immune system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal abscess
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastroenteritis clostridial
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Labyrinthitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Stoma site haemorrhage
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Tendon rupture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Osteonecrosis
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Peripheral motor neuropathy
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Disorientation
Psychiatric disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Ureteral stent removal
Surgical and medical procedures
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Haemorrhage
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Splenic haematoma
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Atrial thrombosis
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cardiac tamponade
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pericarditis
Cardiac disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Choroidal effusion
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Retinal haemorrhage
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Anal fistula
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Colonic fistula
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrointestinal necrosis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrointestinal perforation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Haemorrhoidal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Large intestinal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pneumatosis intestinalis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rectal perforation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Small intestinal perforation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Thrombosis mesenteric vessel
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Death
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Euthanasia
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Influenza like illness
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Multiple organ dysfunction syndrome
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Infusion related hypersensitivity reaction
Immune system disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Bacterial sepsis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Encephalitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Fournier's gangrene
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastroenteritis norovirus
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hepatobiliary infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Infectious pleural effusion
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Influenza
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Intervertebral discitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pelvic abscess
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Perirectal abscess
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Peritonitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pilonidal cyst
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pseudomembranous colitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrointestinal anastomotic leak
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Incision site impaired healing
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Postoperative thoracic procedure complication
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Subdural haematoma
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Amylase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Influenza A virus test positive
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Platelet count decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Lactic acidosis
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Fistula
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Neuroendocrine tumour
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Tumour haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hemiplegia
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Reversible cerebral vasoconstriction syndrome
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Seizure
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Urinary tract obstruction
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypoventilation
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pulmonary thrombosis
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Erythema multiforme
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Paraneoplastic dermatomyositis
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dry gangrene
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Embolism
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Embolism venous
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Peripheral artery occlusion
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Subclavian vein thrombosis
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG00028 events20 affected93 at risk
EG00110 events7 affected40 at risk
EG0022 events1 affected18 at risk
EG003114 events87 affected632 at risk
EG00427 events21 affected293 at risk
EG00513 events8 affected143 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected3 at risk
EG0080 events0 affected2 at risk
EG00962 events49 affected309 at risk
EG01010 events8 affected64 at risk
EG0111 events1 affected34 at risk
EG0121 events1 affected11 at risk
Leukopenia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0006 events5 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG00031 events22 affected93 at risk
EG0012 events2 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 23.1
Systematic Assessment
EG0005 events4 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cataract
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0005 events4 affected93 at risk
EG0015 events4 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Conjunctival haemorrhage
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Periorbital oedema
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Visual impairment
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG00034 events28 affected93 at risk
EG00110 events8 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG00014 events12 affected93 at risk
EG0012 events2 affected40 at risk
EG0023 events3 affected18 at risk
EG003
Angular cheilitis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG00027 events23 affected93 at risk
EG0016 events5 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dental cyst
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG000104 events52 affected93 at risk
EG00143 events16 affected40 at risk
EG0025 events4 affected18 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0009 events7 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0008 events4 affected93 at risk
EG0014 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0013 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0007 events7 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG000106 events53 affected93 at risk
EG00123 events16 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Palatal ulcer
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0004 events4 affected93 at risk
EG0012 events2 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG00036 events24 affected93 at risk
EG0016 events5 affected40 at risk
EG0023 events3 affected18 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG00046 events29 affected93 at risk
EG00112 events8 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Asthenia
General disorders
MedDRA 23.1
Systematic Assessment
EG00032 events20 affected93 at risk
EG0019 events5 affected40 at risk
EG0022 events1 affected18 at risk
EG003
Face oedema
General disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Fatigue
General disorders
MedDRA 23.1
Systematic Assessment
EG00050 events31 affected93 at risk
EG00111 events9 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Influenza like illness
General disorders
MedDRA 23.1
Systematic Assessment
EG0005 events5 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Malaise
General disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 23.1
Systematic Assessment
EG00022 events16 affected93 at risk
EG0018 events7 affected40 at risk
EG0024 events2 affected18 at risk
EG003
Oedema peripheral
General disorders
MedDRA 23.1
Systematic Assessment
EG00013 events9 affected93 at risk
EG0016 events3 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pain
General disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0013 events3 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pyrexia
General disorders
MedDRA 23.1
Systematic Assessment
EG00020 events19 affected93 at risk
EG0018 events8 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0013 events3 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0022 events1 affected18 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0006 events5 affected93 at risk
EG0013 events3 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Cystitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Device related infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Eye infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Folliculitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG00011 events8 affected93 at risk
EG0018 events6 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0004 events4 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Onychomycosis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Paronychia
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG00022 events8 affected93 at risk
EG00113 events5 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Tracheitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0006 events5 affected93 at risk
EG0014 events3 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0006 events6 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0006 events5 affected93 at risk
EG0013 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0007 events5 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Amylase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0009 events6 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0003 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0006 events4 affected93 at risk
EG0013 events2 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0008 events5 affected93 at risk
EG0016 events4 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Lipase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0004 events4 affected93 at risk
EG0013 events3 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Platelet count decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG0007 events4 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Weight decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG00012 events11 affected93 at risk
EG0014 events4 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Weight increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG00026 events20 affected93 at risk
EG00110 events8 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Food craving
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0005 events4 affected93 at risk
EG0013 events2 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG00020 events13 affected93 at risk
EG0016 events3 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0009 events7 affected93 at risk
EG0016 events6 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG00048 events28 affected93 at risk
EG00130 events18 affected40 at risk
EG0025 events3 affected18 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG00017 events15 affected93 at risk
EG0015 events5 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0004 events4 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Muscle tightness
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG00018 events13 affected93 at risk
EG0018 events6 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG00011 events8 affected93 at risk
EG00110 events7 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG00011 events6 affected93 at risk
EG0014 events4 affected40 at risk
EG0022 events1 affected18 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG00011 events9 affected93 at risk
EG0014 events4 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Headache
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG00010 events7 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG00011 events10 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Neurotoxicity
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG00015 events9 affected93 at risk
EG0013 events3 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG00029 events20 affected93 at risk
EG0014 events4 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Peripheral motor neuropathy
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0005 events3 affected93 at risk
EG0013 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG00033 events26 affected93 at risk
EG0015 events4 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Polyneuropathy
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Restless legs syndrome
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Sensory loss
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0002 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 23.1
Systematic Assessment
EG0007 events6 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 23.1
Systematic Assessment
EG00014 events14 affected93 at risk
EG0012 events2 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG00012 events11 affected93 at risk
EG0016 events5 affected40 at risk
EG0023 events3 affected18 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0007 events6 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG00011 events8 affected93 at risk
EG0012 events2 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG00024 events18 affected93 at risk
EG0014 events4 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Nasal dryness
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Nasal ulcer
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 23.1
Systematic Assessment
EG0007 events6 affected93 at risk
EG0012 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00010 events9 affected93 at risk
EG0011 events1 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00014 events12 affected93 at risk
EG00113 events11 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00027 events21 affected93 at risk
EG00116 events12 affected40 at risk
EG0023 events3 affected18 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00019 events11 affected93 at risk
EG00111 events8 affected40 at risk
EG0024 events1 affected18 at risk
EG003
Nail ridging
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Onychoclasis
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0013 events3 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00019 events16 affected93 at risk
EG0015 events5 affected40 at risk
EG0025 events4 affected18 at risk
EG003
Photosensitivity reaction
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00011 events10 affected93 at risk
EG00110 events9 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00010 events10 affected93 at risk
EG0015 events5 affected40 at risk
EG0022 events2 affected18 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00024 events20 affected93 at risk
EG00117 events13 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0004 events3 affected93 at risk
EG0014 events3 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0013 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Skin disorder
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Skin exfoliation
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Skin fissures
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG00012 events8 affected93 at risk
EG00111 events7 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Skin toxicity
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0009 events6 affected93 at risk
EG0017 events4 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypertension
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG00021 events16 affected93 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected18 at risk
EG003
Hypotension
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0008 events8 affected93 at risk
EG0014 events4 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Auditory meatus external erosion
Ear and labyrinth disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dry eye
Eye disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Anal haemorrhage
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cheilitis
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Eructation
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0004 events4 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Catheter site pain
General disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
General physical health deterioration
General disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hepatomegaly
Hepatobiliary disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Anal abscess
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Febrile infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Vascular device infection
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Vulvitis
Infections and infestations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Gastrointestinal stoma complication
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Lumbar vertebral fracture
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0004 events4 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blood potassium decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Body temperature increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cardiac murmur
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 23.1
Systematic Assessment
EG00017 events13 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 23.1
Systematic Assessment
EG0002 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Osteoporosis
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Osteoporotic fracture
Musculoskeletal and connective tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Melanocytic naevus
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Ageusia
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Taste disorder
Nervous system disorders
MedDRA 23.1
Systematic Assessment
EG0004 events4 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Device occlusion
Product Issues
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Depression
Psychiatric disorders
MedDRA 23.1
Systematic Assessment
EG0003 events3 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0007 events5 affected93 at risk
EG0012 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blister
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Decubitus ulcer
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Dermal cyst
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Erythema nodosum
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hair texture abnormal
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Hand dermatitis
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events2 affected93 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Rosacea
Skin and subcutaneous tissue disorders
MedDRA 23.1
Systematic Assessment
EG0002 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Phlebitis
Vascular disorders
MedDRA 23.1
Systematic Assessment
EG0003 events2 affected93 at risk
EG0012 events1 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Stoma site pain
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Wound dehiscence
Injury, poisoning and procedural complications
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 23.1
Systematic Assessment
EG0001 events1 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Tumour associated fever
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.1
Systematic Assessment
EG0000 events0 affected93 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected18 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Preterm newborn infants (gestational age < 37 wks)
BG0000
BG0010
BG0020
BG0030
BG0040
Newborns (0-27 days)
BG0000
BG0010
BG0020
BG0030
BG0040
Infants and toddlers (28 days-23 months)
BG0000
BG0010
BG0020
BG0030
BG0040
Children (2-11 years)
BG0000
BG0010
BG0020
BG0030
BG0040
Adolescents (12-17 years)
BG0000
BG0010
BG0020
BG0030
BG0040
Adults (18-64 years)
BG00058
BG001351
BG0026
BG003199
BG004614
From 65-84 years
BG00035
BG001279
BG0020
BG003110
BG004424
85 years and over
BG0000
BG0015
BG0020
BG0031
BG0046
4
BG003123
BG004423
Male
BG00044
BG001388
BG0022
BG003187
BG004621
1
BG00349
BG004107
Not Hispanic or Latino
BG00075
BG001494
BG0024
BG003247
BG004820
Unknown or Not Reported
BG00013
BG00189
BG0021
BG00314
BG004117
0
BG00314
BG00424
Asian
BG0005
BG00115
BG0020
BG00316
BG00436
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0031
BG0041
Black or African American
BG0000
BG00110
BG0020
BG0035
BG00415
White
BG00076
BG001539
BG0026
BG003264
BG004885
More than one race
BG0000
BG0010
BG0020
BG0031
BG0041
Unknown or Not Reported
BG00011
BG00162
BG0020
BG0039
BG00482
148
OG0043
OG0052
OG00665
OG00734
7.36
(5.82 to 8.94)
OG0044.44(3.55 to 14.69)
OG0054.04(4.04 to 5.39)
OG0063.75(3.42 to 3.91)
OG0077.79(3.98 to 9.46)
Hazard Ratio (HR)
0.95
2-Sided
95
0.77
1.18
Superiority
OG006
OG007
Log Rank
= 0.128
Hazard Ratio (HR)
1.44
2-Sided
95
0.90
2.29
Superiority
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG003
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG005
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG007
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Units
Counts
Participants
OG00040
OG00120
OG002297
OG003148
OG0043
OG0052
OG00665
OG00734
Title
Denominators
Categories
Title
Measurements
OG00024.02(16.07 to 34.00)
OG00121.73(7.92 to 37.19)
OG00222.54(20.04 to 26.87)
OG00322.24(18.50 to 25.13)
OG004NA(NA to 16.07)not evaluable
OG00514.59(NA to NA)not evaluable
OG00622.60(14.23 to 27.40)
OG00725.17(15.90 to 32.59)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
= 0.276
Hazard Ratio (HR)
0.71
2-Sided
95
0.39
1.32
Superiority
OG002
OG003
Log Rank
= 0.076
Hazard Ratio (HR)
0.81
2-Sided
95
0.64
1.02
Superiority
OG004
OG005
Log Rank
= 0.157
Superiority
OG006
OG007
Log Rank
= 0.415
Hazard Ratio (HR)
1.25
2-Sided
95
0.73
2.14
Superiority
OG002
Cohort 1 Control: 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG003
Cohort 2 (IP)
Included participants with BRAFwt. All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
OG004
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG005
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 3 (IP)
Included participants with human epidermal growth factor receptor 2 positive (HER2+). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG008
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG009
Cohort 4 (IP)
Included participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All study participants received either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab during Induction Treatment.
OG010
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG011
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG012
Early Progressing BRAFmut Cohort
BRAFmut participants experiencing early disease progression during induction treatment had the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor was MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor was MSI-H. This cohort was followed during the study, but was not part of the Maintenance Phase study objectives.
Units
Counts
Participants
OG00093
OG00140
OG00218
OG003631
OG004293
OG005143
OG0066
OG0073
OG0082
OG009309
OG01064
OG01134
OG01211
Title
Denominators
Categories
Title
Measurements
OG00098.9
OG001100
OG00294.4
OG00396.0
OG00495.6
OG00588.1
OG006100
OG007100
OG008100
OG00997.4
OG01098.4
OG01188.2
OG01290.9
OG002
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG003
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG005
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG007
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Units
Counts
Participants
OG00040
OG00120
OG002297
OG003148
OG0043
OG0052
OG00665
OG00734
Title
Denominators
Categories
Title
Measurements
OG00020
OG0015
OG00249
OG00322
OG0041
OG0050
OG0067
OG0078
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
= 0.064
Superiority
OG002
OG003
Chi-squared
= 0.658
Superiority
OG006
OG007
Chi-squared
0.093
Superiority
Cohort 1 Control(MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG002
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG003
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG005
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG007
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Units
Counts
Participants
OG00040
OG00120
OG002297
OG003148
OG0043
OG0052
OG00665
OG00734
Title
Denominators
Categories
Title
Measurements
OG00036
OG00115
OG002227
OG003111
OG0041
OG0050
OG00644
OG00726
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
= 0.125
Superiority
OG002
OG003
Chi-squared
= 0.739
Superiority
OG006
OG007
Chi-squared
0.362
Superiority
OG002
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG003
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG005
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG007
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Units
Counts
Participants
OG00040
OG00120
OG002297
OG003148
OG0043
OG0052
OG00665
OG00734
Title
Denominators
Categories
Title
Measurements
OG0003.943(1.18 to 29.70)
OG0015.552(1.38 to 8.02)
OG0025.224(1.22 to 26.74)
OG0034.616(1.25 to 19.91)
OG0045.490(5.490 to 5.490)
OG0050(0 to 0)
OG0063.745(1.77 to 14.92)
OG0072.530(1.64 to 11.83)
OG002
Cohort 2 (MP):5-FU/LV or Capecitabine,Bevacizumab,Atezolizumab
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG003
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG005
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG007
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Units
Counts
Participants
OG00040
OG00120
OG002297
OG003148
OG0043
OG0052
OG00665
OG00734
Title
Denominators
Categories
Title
Measurements
OG00011.50(7.66 to 21.49)
OG0018.74(5.36 to 19.02)
OG0029.30(5.55 to 11.30)
OG0037.59(6.93 to 13.90)
OG0049.205(9.205 to 9.205)
OG0050(0 to 0)
OG0067.11(1.48 to NA)Upper value of the 95% CI cannot be calculated because it is above the maximum value observed.
OG0076.06(2.20 to 7.33)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
= 0.421
Superiority
OG002
OG003
Log Rank
= 0.495
Superiority
OG006
OG007
Log Rank
0.357
Superiority
Participants with BRAFwt received fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG003
Cohort 2 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Participants with human epidermal growth factor receptor 2 positive (HER2+) received 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
OG005
Cohort 3 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
OG006
Cohort 4 (MP): Cobimetinib,Atezolizumab
Participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) received 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
OG007
Cohort 4 Control (MP): 5-FU/LV or Capecitabin, Bevacizumab
Per Investigator discretion, participants received fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.