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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02788279

Recruitment Status : Completed

First Posted : June 2, 2016

Results First Posted : June 18, 2019

Last Update Posted : December 11, 2019

View this study on the modernized ClinicalTrials.gov

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

Participant Flow

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
Arm/Group Description	Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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)

Baseline Characteristics

Arm/Group Title		Regorafenib	Cobimetinib + Atezolizumab	Atezolizumab	Total
Arm/Group Description		Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...	Total of all reporting groups
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
Baseline Analysis Population Description		[Not Specified]
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%

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	Overall survival is defined as the time (in months) between the date o...
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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population.


Arm/Group Title	Regorafenib	Cobimetinib + Atezolizumab	Atezolizumab
Arm/Group Description:	Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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)

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.

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.

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.

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)
Description	PFS was defined as the time from randomization to disease progression ...
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)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population.


Arm/Group Title	Regorafenib	Cobimetinib + Atezolizumab	Atezolizumab
Arm/Group Description:	Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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)

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.

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.

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.

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
Description	PR was defined as at least a 30% decrease in the sum of diameters of t...
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)

Outcome Measure Data

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
Arm/Group Description:	Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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)

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.

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
Description	DOR is defined as the period measured from the date of the first occur...
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)

Outcome Measure Data

Analysis Population Description

DOR was assessed in participants who had an objective response during the study.


Arm/Group Title	Regorafenib	Cobimetinib + Atezolizumab	Atezolizumab
Arm/Group Description:	Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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
Description	The EORTC QLQ-C30 questionnaire consisted of 30 questions generating f...
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)

Outcome Measure Data

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
Arm/Group Description:		Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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
Week 3				-1.50 (10.56)
Week 4	Number Analyzed	44 participants	100 participants	0 participants
Week 4		-6.52 (13.90)	-3.92 (11.05)
Week 6	Number Analyzed	0 participants	0 participants	48 participants
Week 6				-0.14 (12.49)
Week 8	Number Analyzed	29 participants	78 participants	0 participants
Week 8		-8.97 (13.95)	-3.23 (16.15)
Week 9	Number Analyzed	0 participants	0 participants	32 participants
Week 9				-6.67 (17.19)
Week 12	Number Analyzed	24 participants	52 participants	25 participants
Week 12		-7.78 (13.57)	-5.10 (15.54)	-6.40 (16.61)
Week 15	Number Analyzed	0 participants	0 participants	16 participants
Week 15				-7.08 (14.90)
Week 16	Number Analyzed	19 participants	30 participants	0 participants
Week 16		-9.12 (17.10)	-5.11 (16.67)
Week 18	Number Analyzed	0 participants	0 participants	9 participants
Week 18				-3.70 (14.95)
Week 20	Number Analyzed	16 participants	23 participants	0 participants
Week 20		-7.92 (19.51)	-0.87 (14.95)
Week 21	Number Analyzed	0 participants	0 participants	8 participants
Week 21				-8.33 (17.37)
Week 24	Number Analyzed	11 participants	20 participants	6 participants
Week 24		-5.45 (9.81)	-3.00 (18.67)	0.00 (16.87)
Week 27	Number Analyzed	0 participants	0 participants	7 participants
Week 27				0.95 (15.60)
Week 28	Number Analyzed	8 participants	19 participants	0 participants
Week 28		-5.00 (9.92)	-3.16 (15.29)
Week 30	Number Analyzed	0 participants	0 participants	5 participants
Week 30				-8.00 (20.76)
Week 32	Number Analyzed	10 participants	18 participants	0 participants
Week 32		-4.67 (11.35)	-10.74 (21.10)
Week 33	Number Analyzed	0 participants	0 participants	4 participants
Week 33				-1.67 (13.74)
Week 36	Number Analyzed	6 participants	15 participants	3 participants
Week 36		-12.22 (14.25)	-1.78 (16.23)	4.44 (15.40)
Week 39	Number Analyzed	0 participants	0 participants	3 participants
Week 39				2.22 (19.25)
Week 40	Number Analyzed	4 participants	11 participants	0 participants
Week 40		-5.00 (11.39)	-0.61 (16.18)
Week 42	Number Analyzed	0 participants	0 participants	3 participants
Week 42				4.44 (15.40)
Week 44	Number Analyzed	4 participants	14 participants	0 participants
Week 44		1.67 (3.33)	3.33 (16.07)
Week 45	Number Analyzed	0 participants	0 participants	3 participants
Week 45				4.44 (15.40)
Week 48	Number Analyzed	3 participants	11 participants	2 participants
Week 48		-13.33 (6.67)	1.82 (9.47)	0.00 (18.86)
Week 51	Number Analyzed	0 participants	0 participants	2 participants
Week 51				0.00 (18.86)
Week 52	Number Analyzed	4 participants	11 participants	0 participants
Week 52		-5.00 (6.38)	3.64 (10.05)
Week 54	Number Analyzed	0 participants	0 participants	2 participants
Week 54				0.00 (18.86)
Week 56	Number Analyzed	3 participants	8 participants	0 participants
Week 56		-2.22 (3.85)	5.00 (13.69)
Week 57	Number Analyzed	0 participants	0 participants	2 participants
Week 57				0.00 (18.86)
Week 60	Number Analyzed	2 participants	9 participants	2 participants
Week 60		-3.33 (4.71)	2.96 (11.60)	0.00 (18.86)
Week 64	Number Analyzed	2 participants	5 participants	0 participants
Week 64		-6.67 (18.86)	-2.67 (10.11)
Week 68	Number Analyzed	0 participants	1 participants	0 participants
Week 68			0.00 (0.00)
Treatment Discontinuation	Number Analyzed	40 participants	66 participants	39 participants
Treatment Discontinuation		-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
Long Term Follow Up Month 3		-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
Long Term Follow Up Month 6		-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
Long Term Follow Up Month 30			-20.00 ^[1] (NA)	13.33 ^[1] (NA)
Long Term Follow Up Month 33	Number Analyzed	0 participants	1 participants	1 participants
Long Term Follow Up Month 33			-20.00 ^[1] (NA)	13.33 ^[1] (NA)
Long Term Follow Up Month 36	Number Analyzed	0 participants	1 participants	1 participants
Long Term Follow Up Month 36			-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
Description	The EORTC QLQ-C30 questionnaire consisted of 30 questions generating f...
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)

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Regorafenib	Cobimetinib + Atezolizumab	Atezolizumab
Arm/Group Description:		Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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
Week 3				-1.70 (17.76)
Week 4	Number Analyzed	44 participants	100 participants	0 participants
Week 4		-6.44 (18.84)	-7.00 (21.24)
Week 6	Number Analyzed	0 participants	0 participants	48 participants
Week 6				-4.86 (17.43)
Week 8	Number Analyzed	29 participants	78 participants	0 participants
Week 8		-8.05 (15.98)	-4.38 (22.58)
Week 9	Number Analyzed	0 participants	0 participants	31 participants
Week 9				-4.84 (15.78)
Week 12	Number Analyzed	24 participants	51 participants	25 participants
Week 12		-1.04 (18.60)	-4.25 (18.51)	-3.67 (15.42)
Week 15	Number Analyzed	0 participants	0 participants	16 participants
Week 15				-4.69 (12.16)
Week 16	Number Analyzed	20 participants	30 participants	0 participants
Week 16		-4.39 (18.08)	-1.94 (23.64)
Week 18	Number Analyzed	0 participants	0 participants	9 participants
Week 18				7.41 (18.37)
Week 20	Number Analyzed	16 participants	23 participants	0 participants
Week 20		0.52 (18.38)	4.71 (23.28)
Week 21	Number Analyzed	0 participants	0 participants	8 participants
Week 21				6.25 (19.29)
Week 24	Number Analyzed	11 participants	20 participants	6 participants
Week 24		-3.79 (20.19)	3.75 (23.95)	-6.94 (19.31)
Week 27	Number Analyzed	0 participants	0 participants	7 participants
Week 27				-2.38 (19.07)
Week 28	Number Analyzed	8 participants	19 participants	0 participants
Week 28		-8.33 (17.25)	0.00 (31.18)
Week 30	Number Analyzed	0 participants	0 participants	5 participants
Week 30				5.00 (15.14)
Week 32	Number Analyzed	10 participants	18 participants	0 participants
Week 32		-5.00 (14.80)	1.39 (23.79)
Week 33	Number Analyzed	0 participants	0 participants	4 participants
Week 33				6.25 (17.18)
Week 36	Number Analyzed	6 participants	15 participants	3 participants
Week 36		0.00 (7.45)	5.56 (16.86)	16.67 (25.00)
Week 39	Number Analyzed	0 participants	0 participants	3 participants
Week 39				22.22 (17.35)
Week 40	Number Analyzed	4 participants	11 participants	0 participants
Week 40		2.08 (10.49)	11.36 (12.51)
Week 42	Number Analyzed	0 participants	0 participants	3 participants
Week 42				25.00 (16.67)
Week 44	Number Analyzed	4 participants	14 participants	0 participants
Week 44		0.00 (13.61)	9.52 (15.63)
Week 45	Number Analyzed	0 participants	0 participants	3 participants
Week 45				19.44 (9.62)
Week 48	Number Analyzed	3 participants	11 participants	2 participants
Week 48		-2.78 (4.81)	10.61 (15.85)	8.33 (0.00)
Week 51	Number Analyzed	0 participants	0 participants	2 participants
Week 51				8.33 (0.00)
Week 52	Number Analyzed	4 participants	11 participants	0 participants
Week 52		4.17 (15.96)	12.12 (17.62)
Week 54	Number Analyzed	0 participants	0 participants	2 participants
Week 54				12.50 (5.89)
Week 56	Number Analyzed	3 participants	8 participants	0 participants
Week 56		-5.56 (9.62)	18.75 (9.71)
Week 57	Number Analyzed	0 participants	0 participants	2 participants
Week 57				8.33 (0.00)
Week 60	Number Analyzed	2 participants	9 participants	2 participants
Week 60		-4.17 (17.68)	16.67 (15.59)	8.33 (0.00)
Week 64	Number Analyzed	2 participants	5 participants	0 participants
Week 64		-4.17 (5.89)	6.67 (24.58)
Week 68	Number Analyzed	0 participants	1 participants	0 participants
Week 68			0.00 ^[1] (NA)
Treatment Discontinuation	Number Analyzed	39 participants	66 participants	39 participants
Treatment Discontinuation		-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
Long Term Follow-up Month 3		-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
Long Term Follow-up Month 6		-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
Long Term Follow-up Month 30			0.00 ^[1] (NA)	8.33 ^[1] (NA)
Long Term Follow-up Month 33	Number Analyzed	0 participants	1 participants	1 participants
Long Term Follow-up Month 33			0.00 ^[1] (NA)	8.33 ^[1] (NA)
Long Term Follow-up Month 36	Number Analyzed	0 participants	1 participants	1 participants
Long Term Follow-up Month 36			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)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, end of the study (up to approximately 2.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SAF population.


Arm/Group Title	Regorafenib	Cobimetinib + Atezolizumab	Atezolizumab
Arm/Group Description:	Participants received regorafenib 1...	Participants received cobimetinib 6...	Participants received atezolizumab ...
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
Description	[Not Specified]
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).

Outcome Measure Data

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
Arm/Group Description:		Participants received cobimetinib 6...
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
Cycle 1 Day 15 - Predose		195 (190.0%)
Cycle 1 Day 15 - Postdose	Number Analyzed	122 participants
Cycle 1 Day 15 - Postdose		362 (89.4%)
Cycle 4 Day 15 - Predose	Number Analyzed	51 participants
Cycle 4 Day 15 - Predose		94.3 (741.9%)
Cycle 4 Day 15 - Postdose	Number Analyzed	44 participants
Cycle 4 Day 15 - Postdose		210 (273.4%)

9.Secondary Outcome


Title	Serum Concentration of Atezolizumab
Description	Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4; 30 minutes post-infu...
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.

Outcome Measure Data

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
Arm/Group Description:		Participants received atezolizumab ...	Participants received cobimetinib 6...
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
Cycle 1 Day 1 - Predose		NA ^[1] (NA%)	NA ^[1] (NA%)
Cycle 1 Day 1 - 30 min post dose	Number Analyzed	81 participants	164 participants
Cycle 1 Day 1 - 30 min post dose		348 (150.0%)	259 (141.0%)
Cycle 2 Day 1 - Predose	Number Analyzed	73 participants	139 participants
Cycle 2 Day 1 - Predose		81.5 (35.7%)	68.2 (191.2%)
Cycle 2 Day 1 - 30 min post dose	Number Analyzed	1 participants	0 participants
Cycle 2 Day 1 - 30 min post dose		56.2 ^[2] (NA%)
Cycle 3 Day 1 - Predose	Number Analyzed	65 participants	85 participants
Cycle 3 Day 1 - Predose		118 (45.4%)	133 (51.2%)
Cycle 4 Day 1 - Predose	Number Analyzed	37 participants	65 participants
Cycle 4 Day 1 - Predose		146 (52.4%)	167 (48.4%)
Cycle 4 Day 1 - 30 min post dose	Number Analyzed	35 participants	57 participants
Cycle 4 Day 1 - 30 min post dose		487 (41.5%)	415 (37.2%)
Cycle 5 Day 1 - Predose	Number Analyzed	1 participants	0 participants
Cycle 5 Day 1 - Predose		155 ^[2] (NA%)
Cycle 5 Day 1 - 30 min post dose	Number Analyzed	1 participants	0 participants
Cycle 5 Day 1 - 30 min post dose		456 ^[2] (NA%)
Cycle 8 Day 1 - Predose	Number Analyzed	11 participants	22 participants
Cycle 8 Day 1 - Predose		138 (54.6%)	198 (52.6%)
Cycle 16 Day 1 - Predose	Number Analyzed	3 participants	1 participants
Cycle 16 Day 1 - Predose		226 (24.4%)	264 ^[2] (NA%)
Treatment Discontinuation	Number Analyzed	49 participants	102 participants
Treatment Discontinuation		97.9 (114.5%)	76.6 (184.9%)
Unscheduled	Number Analyzed	18 participants	27 participants
Unscheduled		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
Description	[Not Specified]
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)

Outcome Measure Data

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
Arm/Group Description:	Participants received cobimetinib 6...	Participants received atezolizumab ...
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

Adverse Events

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
Arm/Group Description	Participants received regorafenib 1...		Participants received cobimetinib 6...		Participants received atezolizumab ...
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%)
Serious Adverse Events 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
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

Limitations and Caveats

[Not Specified]

More Information

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.

Eng C, Kim TW, Bendell J, Argiles G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F; IMblaze370 Investigators. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2019 Jun;20(6):849-861. doi: 10.1016/S1470-2045(19)30027-0. Epub 2019 Apr 16. Erratum In: Lancet Oncol. 2019 Jun;20(6):e293.

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

To Top