Trial Outcomes & Findings for Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy and Atezolizumab Monotherapy in Participants With Previously Untreated Advanced Melanoma (NCT NCT03178851)
NCT ID: NCT03178851
Last Updated: 2021-11-19
Results Overview
ORR is defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
155 participants
Primary outcome timeframe
Up to approximately 2 years
Results posted on
2021-11-19
Participant Flow
Participant milestones
| Measure |
Cohort A
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Overall Study
STARTED
|
92
|
11
|
52
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
92
|
11
|
52
|
Reasons for withdrawal
| Measure |
Cohort A
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Overall Study
Death
|
48
|
2
|
25
|
|
Overall Study
Withdrawal by Subject
|
8
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
5
|
2
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
|
Overall Study
Study Termination by Sponsor
|
31
|
7
|
26
|
Baseline Characteristics
Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy and Atezolizumab Monotherapy in Participants With Previously Untreated Advanced Melanoma
Baseline characteristics by cohort
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
Total
n=155 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60.7 Years
STANDARD_DEVIATION 11.8 • n=99 Participants
|
62.3 Years
STANDARD_DEVIATION 9.6 • n=107 Participants
|
61.2 Years
STANDARD_DEVIATION 11.8 • n=206 Participants
|
61.0 Years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
53 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
59 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
102 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
32 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
82 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
118 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
88 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
46 Participants
n=206 Participants
|
145 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 2 yearsORR is defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Investigator-Assessed Objective Response Rate (ORR)
|
12.0 Percentage of Participants
Interval 6.12 to 20.39
|
36.4 Percentage of Participants
Interval 10.93 to 69.21
|
38.5 Percentage of Participants
Interval 25.3 to 52.98
|
PRIMARY outcome
Timeframe: Week 16DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Investigator-Assessed Disease Control Rate (DCR)
|
37.0 Percentage of Participants
Interval 27.12 to 47.66
|
54.5 Percentage of Participants
Interval 23.38 to 83.25
|
46.2 Percentage of Participants
Interval 32.23 to 60.53
|
SECONDARY outcome
Timeframe: Up to approximately 2 yearsDOR is defined as the time from the first occurrence of documented OR to disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Investigator-Assessed Duration of Response (DOR)
|
24.2 Months
Interval 7.4 to 24.2
|
NA Months
Interval 7.8 to
Value is not available due to an insufficient number of participants with the event.
|
NA Months
Interval 20.1 to
Value is not available due to an insufficient number of participants with the event.
|
SECONDARY outcome
Timeframe: Up to approximately 2 yearsOS is defined as the time from Cycle 1, Day 1 to death from any cause.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Overall Survival (OS)
|
12.5 Months
Interval 9.4 to 16.7
|
NA Months
Value is not available due to an insufficient number of participants with the event.
|
22.0 Months
Interval 11.7 to
Value is not available due to an insufficient number of participants with the event.
|
SECONDARY outcome
Timeframe: Up to approximately 2 yearsPFS is defined as the time from Cycle 1, Day 1 to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Investigator-Assessed Progression-Free Survival (PFS)
|
3.7 Months
Interval 3.5 to 5.6
|
9.3 Months
Interval 1.8 to 20.1
|
3.7 Months
Interval 2.1 to 7.4
|
SECONDARY outcome
Timeframe: Cycle 1, Day 15; Day 1 of Cycles 2, 3, 4, 8Population: Pharmacokinetic (PK) analyses were performed on all participants that received at least one dose of study drug and who had at least one evaluable PK sample.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Serum Concentration of Atezolizumab
Cmax - Cycle 1 Day 15
|
271 ug/mL
Geometric Coefficient of Variation 22.1
|
275 ug/mL
Geometric Coefficient of Variation 21.9
|
388 ug/mL
Geometric Coefficient of Variation 20.5
|
|
Serum Concentration of Atezolizumab
Cmin - Cycle 2 Day 1
|
65.3 ug/mL
Geometric Coefficient of Variation 330
|
32.9 ug/mL
Geometric Coefficient of Variation 1540
|
73.2 ug/mL
Geometric Coefficient of Variation 55.0
|
|
Serum Concentration of Atezolizumab
Cmin - Cycle 3 Day 1
|
92.4 ug/mL
Geometric Coefficient of Variation 442
|
37.6 ug/mL
Geometric Coefficient of Variation 7490
|
113 ug/mL
Geometric Coefficient of Variation 47.8
|
|
Serum Concentration of Atezolizumab
Cmin - Cycle 4 Day 1
|
121 ug/mL
Geometric Coefficient of Variation 237
|
83.7 ug/mL
Geometric Coefficient of Variation 844
|
128 ug/mL
Geometric Coefficient of Variation 50.8
|
|
Serum Concentration of Atezolizumab
Cmin - Cycle 8 Day 1
|
210 ug/mL
Geometric Coefficient of Variation 46.8
|
NA ug/mL
Geometric Coefficient of Variation NA
Value unavailable due to insufficient number of evaulable samples.
|
159 ug/mL
Geometric Coefficient of Variation 58.7
|
SECONDARY outcome
Timeframe: Cycle 1, Day 15Population: Pharmacokinetic (PK) analyses were performed on all participants that received at least one dose of study drug and who had at least one evaluable PK sample.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Plasma Concentration of Cobimetinib
Cycle 1 Day 15 - Ctrough
|
165 ug/mL
Geometric Coefficient of Variation 137
|
125 ug/mL
Geometric Coefficient of Variation 86.6
|
—
|
|
Plasma Concentration of Cobimetinib
Cycle 1 Day 15 - Css
|
318 ug/mL
Geometric Coefficient of Variation 75.2
|
208 ug/mL
Geometric Coefficient of Variation 59.6
|
—
|
SECONDARY outcome
Timeframe: Baseline through follow upAn adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Percentage of Participants With Adverse Events
|
98.9 Percentage of Participants
|
100 Percentage of Participants
|
100 Percentage of Participants
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 pre-dose to 120 days after the last dose of study medicationTo evaluate the immune response to atezolizumab the percentage of participants with ADAs to atezolizumab will be determined at baseline and during the study.
Outcome measures
| Measure |
Cohort A
n=92 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 Participants
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Change From Baseline in Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
|
32.5 Percentage of Participants
|
30.0 Percentage of Participants
|
10.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Approximately 2 years for Cohorts A and B and 19 months for Cohort CPopulation: The analysis populations included all participants with measureable disease at baseline as measured by either the investigator or by an IRC.
ORR is defined as the percentage of participants with confirmed objective response (OR), as determined by an independent review committee (IRC) according to RECIST v1.1. Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by an independent review committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Outcome measures
| Measure |
Cohort A
n=44 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Cohort C: Independent-Review-Committee-Assessed (IRC) ORR
|
27.3 Percentage of Participants
Interval 14.96 to 42.79
|
—
|
—
|
SECONDARY outcome
Timeframe: Approximately 21 monthsPopulation: The analysis populations included all participants with measureable disease at baseline as measured by either the investigator or by an IRC.
DCR is defined as the percentage of participants with CR, PR, or stable disease (SD), as determined by an independent review committee (IRC) according to RECIST v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
Outcome measures
| Measure |
Cohort A
n=44 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Cohort C: IRC-Assessed DCR
|
38.6 Percentage of Participants
Interval 24.36 to 54.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Approximately 21 monthsPopulation: The analysis populations included all participants with measureable disease at baseline as measured by either the investigator or by an IRC.
DOR is defined as the time from the first occurrence of documented OR to disease progression, as determined by an independent review committee (IRC) according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Outcome measures
| Measure |
Cohort A
n=52 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Cohort C: IRC-Assessed DOR
|
NA Months
Value is not available due to an insufficient number of participants with the event.
|
—
|
—
|
SECONDARY outcome
Timeframe: Approximately 21 monthsPFS is defined as the time from Cycle 1, Day 1 to the first occurrence of disease progression, as determined by an independent review committee (IRC) according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Outcome measures
| Measure |
Cohort A
n=52 Participants
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Cohort C: IRC-Assessed PFS
|
3.7 Months
Interval 2.1 to 11.7
|
—
|
—
|
Adverse Events
Cohort A
Serious events: 42 serious events
Other events: 90 other events
Deaths: 48 deaths
Cohort B
Serious events: 5 serious events
Other events: 11 other events
Deaths: 2 deaths
Cohort C
Serious events: 15 serious events
Other events: 50 other events
Deaths: 25 deaths
Serious adverse events
| Measure |
Cohort A
n=92 participants at risk
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 participants at risk
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 participants at risk
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.3%
4/92 • Number of events 4 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Blood and lymphatic system disorders
Anaemia
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Cardiac disorders
Cardiomyopathy
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Cardiac disorders
Myocarditis
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Cardiac disorders
Stress cardiomyopathy
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Abdominal pain
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Colitis
|
2.2%
2/92 • Number of events 3 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Oesophagitis
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Small intestinal perforation
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
General disorders
Mucosal inflammation
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
General disorders
Pyrexia
|
4.3%
4/92 • Number of events 4 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
3.8%
2/52 • Number of events 2 • Baseline through follow up
|
|
Hepatobiliary disorders
Hepatitis
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Hepatobiliary disorders
Immune-mediated hepatitis
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Cellulitis
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Encephalitis
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Helicobacter infection
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Meningitis
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Respiratory tract infection
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Sepsis
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Urinary tract infection
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Viral infection
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Wound infection
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Amylase increased
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Aspartase aminotransferase increased
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Blood creatine phosphokinase increased
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Investigations
Lipase increased
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 2 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Encephalitis autoimmune
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Encephalopathy
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Syncope
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Renal and urinary disorders
Acute kidney injury
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Vascular disorders
Deep vein thrombosis
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Vascular disorders
Hypertension
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Vascular disorders
Hypotension
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Infections and infestations
Lung infection
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Infections and infestations
Mastoiditis
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
General disorders
Chest pain
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Septic shock
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Angiogram
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Headache
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Immune-mediated encephalitis
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Infections and infestations
Pneumonia
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon neoplasm
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
|
Vascular disorders
Arterial thrombosis
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
1.9%
1/52 • Number of events 1 • Baseline through follow up
|
Other adverse events
| Measure |
Cohort A
n=92 participants at risk
Participants with disease progression on or after treatment with an anti-PD-1 agent initiated dosing with atezolizumab concurrently with cobimetinib. Participants received intravenous (IV) atezolizumab every two weeks (Q2W) on Days 1 and 15 of all cycles. Participants received oral cobimetinib once daily (QD) on Days 1-21 of each 28-day cycle.
|
Cohort B
n=11 participants at risk
Participants with disease progression on or after treatment with an anti-PD-1 agent received cobimetinib prior to initiating IV atezolizumab treatment on Day 15 of Cycle 1. Participants continued to receive atezolizumab on Days 1 and 15 from Cycle 2 onwards. Oral cobimetinib was given QD on Days 1-21 of each 28-day cycle. Participants in this cohort underwent tumor biopsies before and during treatment.
|
Cohort C
n=52 participants at risk
Participants with advanced melanoma, who had not received previous treatment, received IV atezolizumab monotherapy every 3 weeks (Q3W).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
15.2%
14/92 • Number of events 20 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
28.8%
15/52 • Number of events 19 • Baseline through follow up
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
9.1%
1/11 • Number of events 5 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.4%
5/92 • Number of events 6 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Ear and labyrinth disorders
Eustachian tube dysfunction
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Endocrine disorders
Cushingoid
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Endocrine disorders
Hypothyroidism
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
18.2%
2/11 • Number of events 2 • Baseline through follow up
|
21.2%
11/52 • Number of events 11 • Baseline through follow up
|
|
Eye disorders
Chorioretinopathy
|
5.4%
5/92 • Number of events 7 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Eye disorders
Diplopia
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Eye disorders
Eyelid disorder
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Eye disorders
Iridocyclitis
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Eye disorders
MEK inhibitor-assessed serous retinopathy
|
15.2%
14/92 • Number of events 15 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Eye disorders
Vision blurred
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Eye disorders
Visual impairment
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Abdominal discomfort
|
4.3%
4/92 • Number of events 4 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Abdominal pain
|
7.6%
7/92 • Number of events 7 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
5.8%
3/52 • Number of events 3 • Baseline through follow up
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.3%
4/92 • Number of events 4 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Constipation
|
29.3%
27/92 • Number of events 37 • Baseline through follow up
|
36.4%
4/11 • Number of events 8 • Baseline through follow up
|
17.3%
9/52 • Number of events 11 • Baseline through follow up
|
|
Gastrointestinal disorders
Diarrhoea
|
70.7%
65/92 • Number of events 111 • Baseline through follow up
|
90.9%
10/11 • Number of events 26 • Baseline through follow up
|
17.3%
9/52 • Number of events 10 • Baseline through follow up
|
|
Gastrointestinal disorders
Dry mouth
|
13.0%
12/92 • Number of events 13 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Dyspepsia
|
4.3%
4/92 • Number of events 4 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
4.3%
4/92 • Number of events 4 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Mouth ulceration
|
12.0%
11/92 • Number of events 11 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Nausea
|
52.2%
48/92 • Number of events 67 • Baseline through follow up
|
36.4%
4/11 • Number of events 5 • Baseline through follow up
|
13.5%
7/52 • Number of events 13 • Baseline through follow up
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Stomatitis
|
6.5%
6/92 • Number of events 6 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Gastrointestinal disorders
Vomiting
|
38.0%
35/92 • Number of events 44 • Baseline through follow up
|
27.3%
3/11 • Number of events 4 • Baseline through follow up
|
13.5%
7/52 • Number of events 8 • Baseline through follow up
|
|
General disorders
Asthenia
|
13.0%
12/92 • Number of events 15 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
21.2%
11/52 • Number of events 14 • Baseline through follow up
|
|
General disorders
Chest discomfort
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
General disorders
Chills
|
13.0%
12/92 • Number of events 13 • Baseline through follow up
|
18.2%
2/11 • Number of events 2 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
General disorders
Fatigue
|
45.7%
42/92 • Number of events 49 • Baseline through follow up
|
63.6%
7/11 • Number of events 7 • Baseline through follow up
|
9.6%
5/52 • Number of events 7 • Baseline through follow up
|
|
General disorders
Oedema
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
General disorders
Oedema peripheral
|
17.4%
16/92 • Number of events 20 • Baseline through follow up
|
27.3%
3/11 • Number of events 4 • Baseline through follow up
|
5.8%
3/52 • Number of events 3 • Baseline through follow up
|
|
General disorders
Peripheral swelling
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
9.1%
1/11 • Number of events 2 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
General disorders
Pyrexia
|
40.2%
37/92 • Number of events 47 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
5.8%
3/52 • Number of events 8 • Baseline through follow up
|
|
Hepatobiliary disorders
Autoimmune hepatitis
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Cellulitis
|
6.5%
6/92 • Number of events 6 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Oral candidiasis
|
3.3%
3/92 • Number of events 4 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Infections and infestations
Sinusitis
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
5.8%
3/52 • Number of events 4 • Baseline through follow up
|
|
Infections and infestations
Upper respiratory tract infection
|
6.5%
6/92 • Number of events 6 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
7.7%
4/52 • Number of events 6 • Baseline through follow up
|
|
Infections and infestations
Urinary tract infection
|
14.1%
13/92 • Number of events 14 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
9.6%
5/52 • Number of events 5 • Baseline through follow up
|
|
Injury, poisoning and procedural complications
Fall
|
5.4%
5/92 • Number of events 5 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
7.6%
7/92 • Number of events 13 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 2 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Alanine aminotransferase increased
|
7.6%
7/92 • Number of events 10 • Baseline through follow up
|
36.4%
4/11 • Number of events 6 • Baseline through follow up
|
9.6%
5/52 • Number of events 6 • Baseline through follow up
|
|
Investigations
Aspartate aminotrasferase increased
|
10.9%
10/92 • Number of events 15 • Baseline through follow up
|
36.4%
4/11 • Number of events 4 • Baseline through follow up
|
11.5%
6/52 • Number of events 6 • Baseline through follow up
|
|
Investigations
Blood alkaline phosphatase increased
|
2.2%
2/92 • Number of events 3 • Baseline through follow up
|
18.2%
2/11 • Number of events 3 • Baseline through follow up
|
7.7%
4/52 • Number of events 5 • Baseline through follow up
|
|
Investigations
Blood creatine phosphokinase increased
|
27.2%
25/92 • Number of events 41 • Baseline through follow up
|
18.2%
2/11 • Number of events 3 • Baseline through follow up
|
9.6%
5/52 • Number of events 7 • Baseline through follow up
|
|
Investigations
Blood pressure increased
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Ejection fraction decreased
|
4.3%
4/92 • Number of events 5 • Baseline through follow up
|
9.1%
1/11 • Number of events 2 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Lipase increased
|
7.6%
7/92 • Number of events 11 • Baseline through follow up
|
9.1%
1/11 • Number of events 4 • Baseline through follow up
|
17.3%
9/52 • Number of events 10 • Baseline through follow up
|
|
Investigations
Urine output decreased
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Weight increased
|
0.00%
0/92 • Baseline through follow up
|
18.2%
2/11 • Number of events 2 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Decreased appetite
|
23.9%
22/92 • Number of events 23 • Baseline through follow up
|
18.2%
2/11 • Number of events 2 • Baseline through follow up
|
11.5%
6/52 • Number of events 7 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Dehydration
|
6.5%
6/92 • Number of events 7 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Fluid retention
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
18.2%
2/11 • Number of events 3 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.6%
7/92 • Number of events 8 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
13.5%
7/52 • Number of events 10 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
5.8%
3/52 • Number of events 4 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hyperalbuminaemia
|
4.3%
4/92 • Number of events 6 • Baseline through follow up
|
9.1%
1/11 • Number of events 2 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.7%
8/92 • Number of events 11 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
9.6%
5/52 • Number of events 7 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.6%
7/92 • Number of events 7 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
9.8%
9/92 • Number of events 17 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
8/92 • Number of events 10 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
17.3%
9/52 • Number of events 10 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.8%
9/92 • Number of events 9 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
13.5%
7/52 • Number of events 8 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
7.6%
7/92 • Number of events 8 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
18.2%
2/11 • Number of events 3 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.4%
5/92 • Number of events 5 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.5%
6/92 • Number of events 7 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lip neoplasm
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Nasal neoplasm
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Dizziness
|
14.1%
13/92 • Number of events 14 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Dysgeusia
|
6.5%
6/92 • Number of events 6 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Headache
|
10.9%
10/92 • Number of events 12 • Baseline through follow up
|
18.2%
2/11 • Number of events 2 • Baseline through follow up
|
26.9%
14/52 • Number of events 19 • Baseline through follow up
|
|
Nervous system disorders
Neuropathy peripheral
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Presyncope
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Syncope
|
3.3%
3/92 • Number of events 3 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Nervous system disorders
Taste disorder
|
1.1%
1/92 • Number of events 1 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Psychiatric disorders
Insomnia
|
5.4%
5/92 • Number of events 5 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Renal and urinary disorders
Dysuria
|
4.3%
4/92 • Number of events 4 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.6%
7/92 • Number of events 8 • Baseline through follow up
|
18.2%
2/11 • Number of events 2 • Baseline through follow up
|
9.6%
5/52 • Number of events 5 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.9%
10/92 • Number of events 10 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 5 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
7.6%
7/92 • Number of events 8 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.5%
6/92 • Number of events 6 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
53.3%
49/92 • Number of events 62 • Baseline through follow up
|
63.6%
7/11 • Number of events 11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.4%
5/92 • Number of events 5 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
17.4%
16/92 • Number of events 19 • Baseline through follow up
|
36.4%
4/11 • Number of events 6 • Baseline through follow up
|
9.6%
5/52 • Number of events 7 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.7%
31/92 • Number of events 44 • Baseline through follow up
|
45.5%
5/11 • Number of events 5 • Baseline through follow up
|
11.5%
6/52 • Number of events 6 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
10.9%
10/92 • Number of events 18 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
5.4%
5/92 • Number of events 5 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Vascular disorders
Hypertension
|
6.5%
6/92 • Number of events 6 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
19.2%
10/52 • Number of events 13 • Baseline through follow up
|
|
Vascular disorders
Hypotension
|
7.6%
7/92 • Number of events 9 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
5.8%
3/52 • Number of events 7 • Baseline through follow up
|
|
General disorders
Chest pain
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 3 • Baseline through follow up
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 3 • Baseline through follow up
|
|
Infections and infestations
Bronchitis
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 5 • Baseline through follow up
|
|
Investigations
Amylase increased
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
11.5%
6/52 • Number of events 8 • Baseline through follow up
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
9.6%
5/52 • Number of events 5 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 3 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
7.7%
4/52 • Number of events 7 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
4.3%
4/92 • Number of events 6 • Baseline through follow up
|
9.1%
1/11 • Number of events 2 • Baseline through follow up
|
9.6%
5/52 • Number of events 5 • Baseline through follow up
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
19.2%
10/52 • Number of events 12 • Baseline through follow up
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Psychiatric disorders
Depression
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 4 • Baseline through follow up
|
|
Skin and subcutaneous tissue disorders
Vitiligo
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
13.5%
7/52 • Number of events 11 • Baseline through follow up
|
|
Investigations
Weight decreased
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
11.5%
6/52 • Number of events 7 • Baseline through follow up
|
|
General disorders
Influenza like illness
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 7 • Baseline through follow up
|
|
Infections and infestations
Influenza
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 3 • Baseline through follow up
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
5.8%
3/52 • Number of events 4 • Baseline through follow up
|
|
Infections and infestations
Pneumonia
|
0.00%
0/92 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.2%
2/92 • Number of events 3 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
7.7%
4/52 • Number of events 4 • Baseline through follow up
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.2%
2/92 • Number of events 2 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Eye disorders
Eye pruritis
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
0.00%
0/92 • Baseline through follow up
|
9.1%
1/11 • Number of events 1 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.4%
5/92 • Number of events 5 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
|
Investigations
Blood creatinine increased
|
5.4%
5/92 • Number of events 7 • Baseline through follow up
|
0.00%
0/11 • Baseline through follow up
|
0.00%
0/52 • Baseline through follow up
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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 present ation 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.
- Publication restrictions are in place
Restriction type: OTHER