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Trial record 1 of 1 for:    NCT02788279
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A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)

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ClinicalTrials.gov Identifier: NCT02788279
Recruitment Status : Completed
First Posted : June 2, 2016
Results First Posted : June 18, 2019
Last Update Posted : December 11, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody
Drug: Cobimetinib
Drug: Regorafenib
Enrollment 363
Recruitment Details A total of 490 participants were screened of whom only 363 participants were randomized.
Pre-assignment Details  
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first. Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first. Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Period Title: Overall Study
Started [1] 90 183 90
Received Treatment (Safety Population) 80 179 90
Modified ITT Population [2] 57 125 61
Completed 0 0 0
Not Completed 90 183 90
Reason Not Completed
Death             62             136             72
Withdrawal by Subject             10             15             5
Lost to Follow-up             0             3             2
Sponsor decision             18             29             11
[1]
Intent to treat (ITT) population
[2]
Patient-reported outcome (PRO)
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab Total
Hide Arm/Group Description Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first. Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first. Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first. Total of all reporting groups
Overall Number of Baseline Participants 90 183 90 363
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 90 participants 183 participants 90 participants 363 participants
58.4  (10.3) 58.0  (11.9) 56.7  (10.2) 57.8  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 183 participants 90 participants 363 participants
Female
39
  43.3%
75
  41.0%
31
  34.4%
145
  39.9%
Male
51
  56.7%
108
  59.0%
59
  65.6%
218
  60.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 183 participants 90 participants 363 participants
Hispanic or Latino
9
  10.0%
11
   6.0%
5
   5.6%
25
   6.9%
Not Hispanic or Latino
77
  85.6%
166
  90.7%
82
  91.1%
325
  89.5%
Unknown or Not Reported
4
   4.4%
6
   3.3%
3
   3.3%
13
   3.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 183 participants 90 participants 363 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
12
  13.3%
18
   9.8%
11
  12.2%
41
  11.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.5%
1
   1.1%
2
   0.6%
Black or African American
0
   0.0%
8
   4.4%
2
   2.2%
10
   2.8%
White
71
  78.9%
152
  83.1%
73
  81.1%
296
  81.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
7
   7.8%
4
   2.2%
3
   3.3%
14
   3.9%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time (in months) between the date of randomization and the date of death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame From randomization up to death due to any cause (up to approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT population.
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 90 183 90
Median (95% Confidence Interval)
Unit of Measure: months
8.51
(6.41 to 10.71)
8.87
(7.00 to 10.61)
7.10
(6.05 to 10.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regorafenib, Cobimetinib + Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9871
Comments [Not Specified]
Method Stratified Log-Rank
Comments Stratification factors included extended RAS mutation status and time since diagnosis of first metastasis.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.73 to 1.38
Estimation Comments Hazard ratio was estimated using stratified Cox regression.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regorafenib, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3360
Comments [Not Specified]
Method Stratified Log-Rank
Comments Stratification factors included extended RAS mutation status and time since diagnosis of first metastasis.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.83 to 1.71
Estimation Comments Hazard ratio was estimated using stratified Cox regression.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Regorafenib, Cobimetinib + Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9686
Comments [Not Specified]
Method Unstratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.74 to 1.38
Estimation Comments Hazard ratio was estimated using unstratified Cox regression.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Regorafenib, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3553
Comments [Not Specified]
Method Unstratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.83 to 1.69
Estimation Comments Hazard ratio was estimated using unstratified Cox regression.
2.Secondary Outcome
Title Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Hide Description PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was 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. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame From randomization up to disease progression or death due to any cause (up to approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT population.
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 90 183 90
Median (95% Confidence Interval)
Unit of Measure: months
2.00
(1.87 to 3.61)
1.91
(1.87 to 1.97)
1.94
(1.91 to 2.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regorafenib, Cobimetinib + Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1208
Comments [Not Specified]
Method Stratified Log-Rank
Comments Stratification factors included extended RAS mutation status and time since diagnosis of first metastasis.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.94 to 1.65
Estimation Comments Hazard ratio was estimated using stratified Cox regression.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regorafenib, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0509
Comments [Not Specified]
Method Stratified Log-Rank
Comments Stratification factors included extended RAS mutation status and time since diagnosis of first metastasis.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
1.00 to 1.94
Estimation Comments Hazard ratio was estimated using stratified Cox regression.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Regorafenib, Cobimetinib + Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1726
Comments [Not Specified]
Method Unstratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.92 to 1.60
Estimation Comments Hazard ratio was estimated using unstratified Cox regression.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Regorafenib, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0467
Comments [Not Specified]
Method Unstratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
1.00 to 1.91
Estimation Comments Hazard ratio was estimated using unstratified Cox regression.
3.Secondary Outcome
Title Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1
Hide Description PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Objective response and its 95% CI were calculated using the Clopper-Pearson method.
Time Frame From randomization up to death due to any cause (up to approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on evaluable participants in the ITT population with measurable disease at baseline, as determined by the investigator.
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 90 183 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.2
(0.27 to 7.80)
2.7
(0.89 to 6.26)
2.2
(0.27 to 7.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regorafenib, Cobimetinib + Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Stratified Cochrane-Mantel-Haenszel
Comments Stratification factors included extended RAS mutation status and time since diagnosis of first metastasis.
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
-3.92 to 4.94
Estimation Comments 95% CI for difference in response rates was constructed using Hauck-Anderson method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regorafenib, Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Stratified Cochran-Mantel-Haenszel
Comments Stratification factors included extended RAS mutation status and time since diagnosis of first metastasis.
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-4.89 to 4.89
Estimation Comments 95% CI for difference in response rates was constructed using Hauck-Anderson method.
4.Secondary Outcome
Title Duration of Response (DOR) According to RECIST Version 1.1
Hide Description DOR is defined as the period measured from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented. Disease progression was determined on the basis of investigator assessment with use of RECIST v1.1. Median DOR was estimated using the Kaplan-Meier method, and the 95% CI was calculated using the method of Brookmeyer and Crowley.
Time Frame From first occurrence of CR or PR up to disease progression or death due to any cause (up to approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
DOR was assessed in participants who had an objective response during the study.
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 2 5 2
Median (95% Confidence Interval)
Unit of Measure: months
4.50
(3.61 to 5.39)
1.97
(1.77 to 3.81)
2.81
(1.84 to 3.78)
5.Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score
Hide Description The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time Frame Baseline, end of the study (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed’ signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 57 125 61
Mean (Standard Deviation)
Unit of Measure: units of a scale
Week 3 Number Analyzed 0 participants 0 participants 49 participants
-1.50  (10.56)
Week 4 Number Analyzed 44 participants 100 participants 0 participants
-6.52  (13.90) -3.92  (11.05)
Week 6 Number Analyzed 0 participants 0 participants 48 participants
-0.14  (12.49)
Week 8 Number Analyzed 29 participants 78 participants 0 participants
-8.97  (13.95) -3.23  (16.15)
Week 9 Number Analyzed 0 participants 0 participants 32 participants
-6.67  (17.19)
Week 12 Number Analyzed 24 participants 52 participants 25 participants
-7.78  (13.57) -5.10  (15.54) -6.40  (16.61)
Week 15 Number Analyzed 0 participants 0 participants 16 participants
-7.08  (14.90)
Week 16 Number Analyzed 19 participants 30 participants 0 participants
-9.12  (17.10) -5.11  (16.67)
Week 18 Number Analyzed 0 participants 0 participants 9 participants
-3.70  (14.95)
Week 20 Number Analyzed 16 participants 23 participants 0 participants
-7.92  (19.51) -0.87  (14.95)
Week 21 Number Analyzed 0 participants 0 participants 8 participants
-8.33  (17.37)
Week 24 Number Analyzed 11 participants 20 participants 6 participants
-5.45  (9.81) -3.00  (18.67) 0.00  (16.87)
Week 27 Number Analyzed 0 participants 0 participants 7 participants
0.95  (15.60)
Week 28 Number Analyzed 8 participants 19 participants 0 participants
-5.00  (9.92) -3.16  (15.29)
Week 30 Number Analyzed 0 participants 0 participants 5 participants
-8.00  (20.76)
Week 32 Number Analyzed 10 participants 18 participants 0 participants
-4.67  (11.35) -10.74  (21.10)
Week 33 Number Analyzed 0 participants 0 participants 4 participants
-1.67  (13.74)
Week 36 Number Analyzed 6 participants 15 participants 3 participants
-12.22  (14.25) -1.78  (16.23) 4.44  (15.40)
Week 39 Number Analyzed 0 participants 0 participants 3 participants
2.22  (19.25)
Week 40 Number Analyzed 4 participants 11 participants 0 participants
-5.00  (11.39) -0.61  (16.18)
Week 42 Number Analyzed 0 participants 0 participants 3 participants
4.44  (15.40)
Week 44 Number Analyzed 4 participants 14 participants 0 participants
1.67  (3.33) 3.33  (16.07)
Week 45 Number Analyzed 0 participants 0 participants 3 participants
4.44  (15.40)
Week 48 Number Analyzed 3 participants 11 participants 2 participants
-13.33  (6.67) 1.82  (9.47) 0.00  (18.86)
Week 51 Number Analyzed 0 participants 0 participants 2 participants
0.00  (18.86)
Week 52 Number Analyzed 4 participants 11 participants 0 participants
-5.00  (6.38) 3.64  (10.05)
Week 54 Number Analyzed 0 participants 0 participants 2 participants
0.00  (18.86)
Week 56 Number Analyzed 3 participants 8 participants 0 participants
-2.22  (3.85) 5.00  (13.69)
Week 57 Number Analyzed 0 participants 0 participants 2 participants
0.00  (18.86)
Week 60 Number Analyzed 2 participants 9 participants 2 participants
-3.33  (4.71) 2.96  (11.60) 0.00  (18.86)
Week 64 Number Analyzed 2 participants 5 participants 0 participants
-6.67  (18.86) -2.67  (10.11)
Week 68 Number Analyzed 0 participants 1 participants 0 participants
0.00  (0.00)
Treatment Discontinuation Number Analyzed 40 participants 66 participants 39 participants
-17.00  (19.21) -16.24  (23.49) -11.79  (19.01)
Long Term Follow Up Month 3 Number Analyzed 9 participants 15 participants 11 participants
-22.29  (24.29) -15.11  (16.80) -20.00  (26.67)
Long Term Follow Up Month 6 Number Analyzed 9 participants 10 participants 5 participants
-14.07  (17.14) -10.00  (14.14) -8.00  (15.92)
Long Term Follow Up Month 30 Number Analyzed 0 participants 1 participants 1 participants
-20.00 [1]   (NA) 13.33 [1]   (NA)
Long Term Follow Up Month 33 Number Analyzed 0 participants 1 participants 1 participants
-20.00 [1]   (NA) 13.33 [1]   (NA)
Long Term Follow Up Month 36 Number Analyzed 0 participants 1 participants 1 participants
-20.00 [1]   (NA) 13.33 [1]   (NA)
[1]
The standard deviation is a measure of the amount of variation or dispersion of a set of values. Number analyzed is 1 so SD is not available.
6.Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study
Hide Description The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time Frame Baseline, end of the study (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed’ signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 57 125 61
Mean (Standard Deviation)
Unit of Measure: units of a scale
Week 3 Number Analyzed 0 participants 0 participants 49 participants
-1.70  (17.76)
Week 4 Number Analyzed 44 participants 100 participants 0 participants
-6.44  (18.84) -7.00  (21.24)
Week 6 Number Analyzed 0 participants 0 participants 48 participants
-4.86  (17.43)
Week 8 Number Analyzed 29 participants 78 participants 0 participants
-8.05  (15.98) -4.38  (22.58)
Week 9 Number Analyzed 0 participants 0 participants 31 participants
-4.84  (15.78)
Week 12 Number Analyzed 24 participants 51 participants 25 participants
-1.04  (18.60) -4.25  (18.51) -3.67  (15.42)
Week 15 Number Analyzed 0 participants 0 participants 16 participants
-4.69  (12.16)
Week 16 Number Analyzed 20 participants 30 participants 0 participants
-4.39  (18.08) -1.94  (23.64)
Week 18 Number Analyzed 0 participants 0 participants 9 participants
7.41  (18.37)
Week 20 Number Analyzed 16 participants 23 participants 0 participants
0.52  (18.38) 4.71  (23.28)
Week 21 Number Analyzed 0 participants 0 participants 8 participants
6.25  (19.29)
Week 24 Number Analyzed 11 participants 20 participants 6 participants
-3.79  (20.19) 3.75  (23.95) -6.94  (19.31)
Week 27 Number Analyzed 0 participants 0 participants 7 participants
-2.38  (19.07)
Week 28 Number Analyzed 8 participants 19 participants 0 participants
-8.33  (17.25) 0.00  (31.18)
Week 30 Number Analyzed 0 participants 0 participants 5 participants
5.00  (15.14)
Week 32 Number Analyzed 10 participants 18 participants 0 participants
-5.00  (14.80) 1.39  (23.79)
Week 33 Number Analyzed 0 participants 0 participants 4 participants
6.25  (17.18)
Week 36 Number Analyzed 6 participants 15 participants 3 participants
0.00  (7.45) 5.56  (16.86) 16.67  (25.00)
Week 39 Number Analyzed 0 participants 0 participants 3 participants
22.22  (17.35)
Week 40 Number Analyzed 4 participants 11 participants 0 participants
2.08  (10.49) 11.36  (12.51)
Week 42 Number Analyzed 0 participants 0 participants 3 participants
25.00  (16.67)
Week 44 Number Analyzed 4 participants 14 participants 0 participants
0.00  (13.61) 9.52  (15.63)
Week 45 Number Analyzed 0 participants 0 participants 3 participants
19.44  (9.62)
Week 48 Number Analyzed 3 participants 11 participants 2 participants
-2.78  (4.81) 10.61  (15.85) 8.33  (0.00)
Week 51 Number Analyzed 0 participants 0 participants 2 participants
8.33  (0.00)
Week 52 Number Analyzed 4 participants 11 participants 0 participants
4.17  (15.96) 12.12  (17.62)
Week 54 Number Analyzed 0 participants 0 participants 2 participants
12.50  (5.89)
Week 56 Number Analyzed 3 participants 8 participants 0 participants
-5.56  (9.62) 18.75  (9.71)
Week 57 Number Analyzed 0 participants 0 participants 2 participants
8.33  (0.00)
Week 60 Number Analyzed 2 participants 9 participants 2 participants
-4.17  (17.68) 16.67  (15.59) 8.33  (0.00)
Week 64 Number Analyzed 2 participants 5 participants 0 participants
-4.17  (5.89) 6.67  (24.58)
Week 68 Number Analyzed 0 participants 1 participants 0 participants
0.00 [1]   (NA)
Treatment Discontinuation Number Analyzed 39 participants 66 participants 39 participants
-19.87  (23.93) -14.27  (25.98) -14.53  (20.48)
Long Term Follow-up Month 3 Number Analyzed 9 participants 15 participants 11 participants
-21.30  (28.60) -6.11  (22.15) -11.36  (20.16)
Long Term Follow-up Month 6 Number Analyzed 9 participants 10 participants 5 participants
-13.89  (19.09) -15.83  (15.44) -11.67  (15.14)
Long Term Follow-up Month 30 Number Analyzed 0 participants 1 participants 1 participants
0.00 [1]   (NA) 8.33 [1]   (NA)
Long Term Follow-up Month 33 Number Analyzed 0 participants 1 participants 1 participants
0.00 [1]   (NA) 8.33 [1]   (NA)
Long Term Follow-up Month 36 Number Analyzed 0 participants 1 participants 1 participants
0.00 [1]   (NA) 8.33 [1]   (NA)
[1]
The standard deviation is a measure of the amount of variation or dispersion of a set of values. Number analyzed is 1 so SD is not available.
7.Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs)
Hide Description [Not Specified]
Time Frame Baseline, end of the study (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the SAF population.
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 80 179 90
Measure Type: Number
Unit of Measure: percentage of participants
Serious AEs 23.8 39.7 16.7
Non-serious AEs 97.5 97.8 93.3
8.Secondary Outcome
Title Plasma Concentration of Cobimetinib
Hide Description [Not Specified]
Time Frame Predose (0 hours) and 3 to 6 hours after dose on Day 15 of Cycles 1 and 4 (1 cycle = 28 days) (up to approximately 2.5 years).
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) evaluable population included all participants who received any dose of study medication and who had at least one post-baseline PK sample available. Only included participants in the Cobimetnib arm
Arm/Group Title Cobimetinib + Atezolizumab
Hide Arm/Group Description:
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 124
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram/milliliter (ng/mL)
Cycle 1 Day 15 - Predose Number Analyzed 124 participants
195
(190.0%)
Cycle 1 Day 15 - Postdose Number Analyzed 122 participants
362
(89.4%)
Cycle 4 Day 15 - Predose Number Analyzed 51 participants
94.3
(741.9%)
Cycle 4 Day 15 - Postdose Number Analyzed 44 participants
210
(273.4%)
9.Secondary Outcome
Title Serum Concentration of Atezolizumab
Hide Description Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4; 30 minutes post-infusion on Day 1 of Cycles 1 and 4; pre-infusion (0 hours) on Day 1 of Cycle 8 and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days)
Time Frame Pre-infusion (0 hours) on Day 1 of Cycle 1 up to approximately 2.5 years. Detailed time frame is explained in the outcome measure description field.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) evaluable population included all participants who received any dose of study medication and who had at least one post-baseline PK sample available. Also, only included participants to whom Atezolizumab was administered.
Arm/Group Title Atezolizumab Cobimetinib + Atezolizumab
Hide Arm/Group Description:
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 89 179
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram/milliliter (ug/mL)
Cycle 1 Day 1 - Predose Number Analyzed 84 participants 176 participants
NA [1] 
(NA%)
NA [1] 
(NA%)
Cycle 1 Day 1 - 30 min post dose Number Analyzed 81 participants 164 participants
348
(150.0%)
259
(141.0%)
Cycle 2 Day 1 - Predose Number Analyzed 73 participants 139 participants
81.5
(35.7%)
68.2
(191.2%)
Cycle 2 Day 1 - 30 min post dose Number Analyzed 1 participants 0 participants
56.2 [2] 
(NA%)
Cycle 3 Day 1 - Predose Number Analyzed 65 participants 85 participants
118
(45.4%)
133
(51.2%)
Cycle 4 Day 1 - Predose Number Analyzed 37 participants 65 participants
146
(52.4%)
167
(48.4%)
Cycle 4 Day 1 - 30 min post dose Number Analyzed 35 participants 57 participants
487
(41.5%)
415
(37.2%)
Cycle 5 Day 1 - Predose Number Analyzed 1 participants 0 participants
155 [2] 
(NA%)
Cycle 5 Day 1 - 30 min post dose Number Analyzed 1 participants 0 participants
456 [2] 
(NA%)
Cycle 8 Day 1 - Predose Number Analyzed 11 participants 22 participants
138
(54.6%)
198
(52.6%)
Cycle 16 Day 1 - Predose Number Analyzed 3 participants 1 participants
226
(24.4%)
264 [2] 
(NA%)
Treatment Discontinuation Number Analyzed 49 participants 102 participants
97.9
(114.5%)
76.6
(184.9%)
Unscheduled Number Analyzed 18 participants 27 participants
0.784
(2159.5%)
0.539 [1] 
(NA%)
[1]
If more than one-third values were less than reportable, then only the median and maximum are reported and other summary statistics are displayed as non-reportable.
[2]
The amount of variation is not available as the number analyzed is 1.
10.Secondary Outcome
Title Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Hide Description [Not Specified]
Time Frame Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4, 8, and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the SAF population and included participants with at least one predose and one postdose ATA assessment.
Arm/Group Title Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description:
Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
Overall Number of Participants Analyzed 160 80
Measure Type: Number
Unit of Measure: percentage of participants
43.8 41.3
Time Frame From baseline to end of study (approximately 2.5 years).
Adverse Event Reporting Description ITT was monitored for All-Cause Mortality, the safety analysis set (SAF) was assessed for Serious Adverse Events and Other (Not Including Serious) Adverse Events. SAF included all enrolled participants who received at least one dose of any study medication.
 
Arm/Group Title Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Hide Arm/Group Description Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first. Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first. Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant’s or physician decision to withdraw, or pregnancy, whichever occurs first.
All-Cause Mortality
Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   62/90 (68.89%)      136/183 (74.32%)      72/90 (80.00%)    
Hide Serious Adverse Events
Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/90 (21.11%)      71/183 (38.80%)      15/90 (16.67%)    
Blood and lymphatic system disorders       
ANAEMIA  1  0/80 (0.00%)  0 5/179 (2.79%)  5 0/90 (0.00%)  0
Cardiac disorders       
ATRIAL FIBRILLATION  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
LEFT VENTRICULAR DYSFUNCTION  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
Endocrine disorders       
ADRENAL INSUFFICIENCY  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Eye disorders       
MACULOPATHY  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Gastrointestinal disorders       
ABDOMINAL PAIN  1  2/80 (2.50%)  2 2/179 (1.12%)  2 1/90 (1.11%)  1
ANAL HAEMORRHAGE  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
COLITIS  1  0/80 (0.00%)  0 2/179 (1.12%)  2 1/90 (1.11%)  1
COLONIC FISTULA  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
CONSTIPATION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
DIARRHOEA  1  3/80 (3.75%)  3 6/179 (3.35%)  6 0/90 (0.00%)  0
GASTROINTESTINAL HAEMORRHAGE  1  1/80 (1.25%)  1 1/179 (0.56%)  1 0/90 (0.00%)  0
ILEUS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
INTESTINAL PERFORATION  1  2/80 (2.50%)  2 1/179 (0.56%)  1 0/90 (0.00%)  0
LOWER GASTROINTESTINAL HAEMORRHAGE  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
NAUSEA  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
PANCREATITIS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
RECTAL HAEMORRHAGE  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
SMALL INTESTINAL OBSTRUCTION  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
SUBILEUS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
UPPER GASTROINTESTINAL HAEMORRHAGE  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
VOLVULUS OF SMALL BOWEL  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
VOMITING  1  1/80 (1.25%)  1 1/179 (0.56%)  1 0/90 (0.00%)  0
General disorders       
ASTHENIA  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
CHILLS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
DEATH  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
FATIGUE  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
GENERAL PHYSICAL HEALTH DETERIORATION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
INFLAMMATION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
INFLUENZA LIKE ILLNESS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
MUCOSAL INFLAMMATION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
PYREXIA  1  3/80 (3.75%)  3 12/179 (6.70%)  15 2/90 (2.22%)  2
Hepatobiliary disorders       
AUTOIMMUNE HEPATITIS  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
BILE DUCT OBSTRUCTION  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
CHOLANGITIS  1  0/80 (0.00%)  0 1/179 (0.56%)  2 0/90 (0.00%)  0
Immune system disorders       
HYPERSENSITIVITY  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
Infections and infestations       
ABDOMINAL HERNIA INFECTION  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
BACTERAEMIA  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
BACTERIAL SEPSIS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
INFECTION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
LUNG INFECTION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
ORAL CANDIDIASIS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
PNEUMONIA  1  0/80 (0.00%)  0 2/179 (1.12%)  3 0/90 (0.00%)  0
PNEUMONIA PNEUMOCOCCAL  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
PULMONARY SEPSIS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 1/90 (1.11%)  1
PYELONEPHRITIS  1  1/80 (1.25%)  1 1/179 (0.56%)  1 0/90 (0.00%)  0
PYELONEPHRITIS ACUTE  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
RESPIRATORY TRACT INFECTION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
RHINOVIRUS INFECTION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
SEPSIS  1  2/80 (2.50%)  2 4/179 (2.23%)  4 0/90 (0.00%)  0
STREPTOCOCCAL BACTERAEMIA  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
URINARY TRACT INFECTION  1  0/80 (0.00%)  0 2/179 (1.12%)  2 0/90 (0.00%)  0
Injury, poisoning and procedural complications       
HIP FRACTURE  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
INFUSION RELATED REACTION  1  0/80 (0.00%)  0 3/179 (1.68%)  3 0/90 (0.00%)  0
LUMBAR VERTEBRAL FRACTURE  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
STOMA SITE HAEMORRHAGE  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
Investigations       
BLOOD CREATINE PHOSPHOKINASE INCREASED  1  0/80 (0.00%)  0 2/179 (1.12%)  2 0/90 (0.00%)  0
INFLUENZA A VIRUS TEST POSITIVE  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
INTERNATIONAL NORMALISED RATIO INCREASED  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Metabolism and nutrition disorders       
DECREASED APPETITE  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
DEHYDRATION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
HYPONATRAEMIA  1  1/80 (1.25%)  1 2/179 (1.12%)  2 0/90 (0.00%)  0
Musculoskeletal and connective tissue disorders       
BACK PAIN  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
MUSCULAR WEAKNESS  1  0/80 (0.00%)  0 2/179 (1.12%)  2 1/90 (1.11%)  1
Nervous system disorders       
ATAXIA  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
CEREBROVASCULAR ACCIDENT  1  0/80 (0.00%)  0 2/179 (1.12%)  2 0/90 (0.00%)  0
COGNITIVE DISORDER  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
DIZZINESS  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
ENCEPHALOPATHY  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
GUILLAIN-BARRE SYNDROME  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
METABOLIC ENCEPHALOPATHY  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
NONINFECTIVE ENCEPHALITIS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
SYNCOPE  1  0/80 (0.00%)  0 2/179 (1.12%)  2 0/90 (0.00%)  0
TRANSIENT ISCHAEMIC ATTACK  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Psychiatric disorders       
CONFUSIONAL STATE  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
DELIRIUM  1  0/80 (0.00%)  0 1/179 (0.56%)  1 1/90 (1.11%)  1
SUICIDE ATTEMPT  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Renal and urinary disorders       
ACUTE KIDNEY INJURY  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
NEPHRITIS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
STERILE PYURIA  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Reproductive system and breast disorders       
VAGINAL HAEMORRHAGE  1  1/80 (1.25%)  1 0/179 (0.00%)  0 0/90 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
DYSPNOEA  1  0/80 (0.00%)  0 1/179 (0.56%)  2 1/90 (1.11%)  1
HYPOXIA  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
PLEURAL EFFUSION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 1/90 (1.11%)  1
PNEUMONITIS  1  0/80 (0.00%)  0 1/179 (0.56%)  1 1/90 (1.11%)  1
PNEUMOTHORAX  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Skin and subcutaneous tissue disorders       
RASH  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
Vascular disorders       
HYPOTENSION  1  0/80 (0.00%)  0 1/179 (0.56%)  1 0/90 (0.00%)  0
PELVIC VENOUS THROMBOSIS  1  0/80 (0.00%)  0 0/179 (0.00%)  0 1/90 (1.11%)  1
1
Term from vocabulary, MedDRA version 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Regorafenib Cobimetinib + Atezolizumab Atezolizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   78/80 (97.50%)      173/179 (96.65%)      81/90 (90.00%)    
Blood and lymphatic system disorders       
ANAEMIA  1  8/80 (10.00%)  9 25/179 (13.97%)  28 5/90 (5.56%)  5
THROMBOCYTOPENIA  1  2/80 (2.50%)  2 10/179 (5.59%)  10 0/90 (0.00%)  0
Gastrointestinal disorders       
ABDOMINAL PAIN  1  21/80 (26.25%)  27 30/179 (16.76%)  34 13/90 (14.44%)  19
ABDOMINAL PAIN UPPER  1  2/80 (2.50%)  2 3/179 (1.68%)  3 7/90 (7.78%)  8
CONSTIPATION  1  17/80 (21.25%)  19 33/179 (18.44%)  41 11/90 (12.22%)  12
DIARRHOEA  1  30/80 (37.50%)  59 115/179 (64.25%)  200 17/90 (18.89%)  23
DRY MOUTH  1  4/80 (5.00%)  4 9/179 (5.03%)  9 2/90 (2.22%)  2
DYSPEPSIA  1  0/80 (0.00%)  0 10/179 (5.59%)  10 2/90 (2.22%)  2
NAUSEA  1  12/80 (15.00%)  13 67/179 (37.43%)  93 19/90 (21.11%)  23
PROCTALGIA  1  4/80 (5.00%)  4 2/179 (1.12%)  2 0/90 (0.00%)  0
STOMATITIS  1  13/80 (16.25%)  21 18/179 (10.06%)  18 0/90 (0.00%)  0
VOMITING  1  9/80 (11.25%)  10 52/179 (29.05%)  79 13/90 (14.44%)  15
General disorders       
ASTHENIA  1  17/80 (21.25%)  22 37/179 (20.67%)  54 12/90 (13.33%)  19
CHEST PAIN  1  4/80 (5.00%)  4 5/179 (2.79%)  5 2/90 (2.22%)  2
CHILLS  1  4/80 (5.00%)  4 14/179 (7.82%)  15 4/90 (4.44%)  5
FACE OEDEMA  1  0/80 (0.00%)  0 10/179 (5.59%)  12 0/90 (0.00%)  0
FATIGUE  1  38/80 (47.50%)  46 65/179 (36.31%)  75 24/90 (26.67%)  28
MUCOSAL INFLAMMATION  1  6/80 (7.50%)  8 16/179 (8.94%)  19 4/90 (4.44%)  6
OEDEMA PERIPHERAL  1  3/80 (3.75%)  3 27/179 (15.08%)  32 8/90 (8.89%)  9
PYREXIA  1  20/80 (25.00%)  25 53/179 (29.61%)  67 12/90 (13.33%)  13
Infections and infestations       
UPPER RESPIRATORY TRACT INFECTION  1  3/80 (3.75%)  4 4/179 (2.23%)  6 6/90 (6.67%)  6
URINARY TRACT INFECTION  1  4/80 (5.00%)  8 8/179 (4.47%)  10 2/90 (2.22%)  2
Investigations       
ALANINE AMINOTRANSFERASE INCREASED  1  5/80 (6.25%)  6 10/179 (5.59%)  17 5/90 (5.56%)  5
ASPARTATE AMINOTRANSFERASE INCREASED  1  7/80 (8.75%)  8 16/179 (8.94%)  27 6/90 (6.67%)  8
BLOOD ALKALINE PHOSPHATASE INCREASED  1  1/80 (1.25%)  1 14/179 (7.82%)  14 8/90 (8.89%)  11
BLOOD BILIRUBIN INCREASED  1  4/80 (5.00%)  7 3/179 (1.68%)  3 2/90 (2.22%)  2
BLOOD CREATINE PHOSPHOKINASE INCREASED  1  3/80 (3.75%)  5 22/179 (12.29%)  39 0/90 (0.00%)  0
BLOOD CREATININE INCREASED  1  5/80 (6.25%)  6 3/179 (1.68%)  3 0/90 (0.00%)  0
BLOOD THYROID STIMULATING HORMONE INCREASED  1  4/80 (5.00%)  4 3/179 (1.68%)  5 3/90 (3.33%)  3
LIPASE INCREASED  1  6/80 (7.50%)  7 9/179 (5.03%)  10 1/90 (1.11%)  2
WEIGHT DECREASED  1  17/80 (21.25%)  18 8/179 (4.47%)  9 7/90 (7.78%)  7
Metabolism and nutrition disorders       
DECREASED APPETITE  1  34/80 (42.50%)  40 49/179 (27.37%)  57 21/90 (23.33%)  27
HYPOCALCAEMIA  1  5/80 (6.25%)  5 7/179 (3.91%)  7 2/90 (2.22%)  2
HYPOKALAEMIA  1  3/80 (3.75%)  4 14/179 (7.82%)  17 1/90 (1.11%)  1
HYPOPHOSPHATAEMIA  1  7/80 (8.75%)  7 11/179 (6.15%)  11 3/90 (3.33%)  3
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  5/80 (6.25%)  6 14/179 (7.82%)  14 8/90 (8.89%)  8
BACK PAIN  1  8/80 (10.00%)  10 17/179 (9.50%)  21 13/90 (14.44%)  15
MUSCLE SPASMS  1  6/80 (7.50%)  6 3/179 (1.68%)  3 0/90 (0.00%)  0
MUSCULOSKELETAL PAIN  1  4/80 (5.00%)  4 5/179 (2.79%)  5 2/90 (2.22%)  2
MYALGIA  1  7/80 (8.75%)  10 9/179 (5.03%)  12 3/90 (3.33%)  3
PAIN IN EXTREMITY  1  6/80 (7.50%)  8 12/179 (6.70%)  16 6/90 (6.67%)  6
Nervous system disorders       
DIZZINESS  1  3/80 (3.75%)  3 10/179 (5.59%)  12 0/90 (0.00%)  0
HEADACHE  1  10/80 (12.50%)  12 17/179 (9.50%)  21 11/90 (12.22%)  11
Psychiatric disorders       
INSOMNIA  1  3/80 (3.75%)  3 9/179 (5.03%)  9 6/90 (6.67%)  6
Respiratory, thoracic and mediastinal disorders       
COUGH  1  8/80 (10.00%)  10 33/179 (18.44%)  35 12/90 (13.33%)  12
DYSPHONIA  1  19/80 (23.75%)  27 0/179 (0.00%)  0 1/90 (1.11%)  1
DYSPNOEA  1  13/80 (16.25%)  13 36/179 (20.11%)  41 12/90 (13.33%)  12
EPISTAXIS  1  7/80 (8.75%)  7 9/179 (5.03%)  9 0/90 (0.00%)  0
OROPHARYNGEAL PAIN  1  5/80 (6.25%)  6 7/179 (3.91%)  8 2/90 (2.22%)  2
Skin and subcutaneous tissue disorders       
DERMATITIS ACNEIFORM  1  2/80 (2.50%)  2 46/179 (25.70%)  56 2/90 (2.22%)  3
DRY SKIN  1  1/80 (1.25%)  1 14/179 (7.82%)  14 3/90 (3.33%)  3
ERYTHEMA  1  5/80 (6.25%)  5 2/179 (1.12%)  3 0/90 (0.00%)  0
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME  1  42/80 (52.50%)  70 3/179 (1.68%)  3 1/90 (1.11%)  1
PRURITUS  1  2/80 (2.50%)  2 22/179 (12.29%)  25 3/90 (3.33%)  3
RASH  1  17/80 (21.25%)  19 85/179 (47.49%)  122 8/90 (8.89%)  8
RASH MACULO-PAPULAR  1  3/80 (3.75%)  3 11/179 (6.15%)  12 1/90 (1.11%)  1
Vascular disorders       
HYPERTENSION  1  25/80 (31.25%)  31 9/179 (5.03%)  10 4/90 (4.44%)  6
1
Term from vocabulary, MedDRA version 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02788279    
Other Study ID Numbers: GO30182
2016-000202-11 ( EudraCT Number )
First Submitted: May 27, 2016
First Posted: June 2, 2016
Results First Submitted: March 8, 2019
Results First Posted: June 18, 2019
Last Update Posted: December 11, 2019