Trial Outcomes & Findings for An Investigational Immuno-therapy Study to Evaluate Safety and Effectiveness in Patients With Melanoma That Has Spread to the Brain, Treated With Nivolumab in Combination With Ipilimumab, Followed by Nivolumab by Itself (NCT NCT02320058)
NCT ID: NCT02320058
Last Updated: 2021-10-05
Results Overview
Intracranial Clinical Benefit Rate (CBR) is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of \>6 months, as determined by modified RECIST 1.1 criteria for index intracranial lesions based on investigator review.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
119 participants
Primary outcome timeframe
Up to 66 months
Results posted on
2021-10-05
Participant Flow
119 participants treated
Participant milestones
| Measure |
Cohort A
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
101
|
18
|
|
Overall Study
COMPLETED
|
59
|
5
|
|
Overall Study
NOT COMPLETED
|
42
|
13
|
Reasons for withdrawal
| Measure |
Cohort A
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Overall Study
Death
|
25
|
10
|
|
Overall Study
Lost to Follow-up
|
4
|
0
|
|
Overall Study
Other reasons
|
4
|
1
|
|
Overall Study
Withdrawal by Subject
|
8
|
2
|
|
Overall Study
Not reported
|
1
|
0
|
Baseline Characteristics
An Investigational Immuno-therapy Study to Evaluate Safety and Effectiveness in Patients With Melanoma That Has Spread to the Brain, Treated With Nivolumab in Combination With Ipilimumab, Followed by Nivolumab by Itself
Baseline characteristics by cohort
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Total
n=119 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.0 Years
STANDARD_DEVIATION 12.29 • n=5 Participants
|
58.2 Years
STANDARD_DEVIATION 13.24 • n=7 Participants
|
58.0 Years
STANDARD_DEVIATION 12.38 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
99 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
99 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
116 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Intracranial Clinical Benefit Rate (CBR) is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of \>6 months, as determined by modified RECIST 1.1 criteria for index intracranial lesions based on investigator review.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Intracranial Clinical Benefit Rate (CBR)
|
57.4 Percentage of Participants
Interval 47.2 to 67.2
|
16.7 Percentage of Participants
Interval 3.6 to 41.4
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Investigator-Assessed Intracranial Objective Response Rate (ORR) per modified RECIST 1.1 criteria is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Intracranial Objective Response Rate (ORR)
|
53.5 Percentage of Participants
Interval 43.3 to 63.5
|
16.7 Percentage of Participants
Interval 3.6 to 41.4
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Intracranial progression-free survival (PFS) per modified RECIST 1.1 criteria is defined as the time between the date of first dose of study drug and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participant who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on the date of first dose of study drug. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Intracranial Progression Free Survival (PFS)
|
NA Months
Interval 6.87 to
Median and Upper Limit not reached per the Kaplan-Meier method, as the probability of survival was still above 50%
|
1.18 Months
Interval 0.72 to 1.25
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Extracranial Clinical Benefit Rate (CBR) is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of \>6 months, as determined by RECIST 1.1 criteria for index extracranial lesions based on investigator review.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Extracranial Clinical Benefit Rate (CBR)
|
53.5 Percentage of Participants
Interval 43.3 to 63.5
|
22.2 Percentage of Participants
Interval 6.4 to 47.6
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Extracranial Objective Response Rate (ORR) per RECIST 1.1 criteria is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Extracranial Objective Response Rate (ORR)
|
48.5 Percentage of Participants
Interval 38.4 to 58.7
|
22.2 Percentage of Participants
Interval 6.4 to 47.6
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Extracranial progression-free survival (PFS) per RECIST 1.1 criteria is defined as the time between the date of first dose of study drug and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participant who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on the date of first dose of study drug. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Extracranial Progression Free Survival (PFS)
|
39.29 Months
Interval 16.13 to 45.8
|
1.77 Months
Interval 0.79 to
upper limit of the confidence interval is not yet reached
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Investigator-assessed global (intracranial + extracranial) clinical benefit rate (CBR) per a combination of modified RECIST 1.1 criteria for intracranial lesions and RECIST 1.1 for extracranial disease is defined as the percentage of all treated participants whose best overall response is either a complete response (CR) or partial response (PR) or whose best overall response was Stable Disease (SD) with duration of \>6 months
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Global Clinical Benefit Rate (CBR)
|
55.4 Percentage of participants
Interval 45.2 to 65.3
|
22.2 Percentage of participants
Interval 6.4 to 47.6
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Investigator-assessed global objective response rate (ORR) per a combination of modified RECIST 1.1 criteria for intracranial lesions and RECIST 1.1 for extracranial disease is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Global Objective Response Rate (ORR)
|
51.5 Percentage of participants
Interval 41.3 to 61.6
|
22.2 Percentage of participants
Interval 6.4 to 47.6
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Investigator-assessed global progression free survival (PFS) per a combination of modified RECIST 1.1 criteria for intracranial lesions and RECIST 1.1 for extracranial disease is defined as the time between the date of first dose of study drug and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participant who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on the date of first dose of study drug. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Global Progression Free Survival (PFS)
|
29.54 Months
Interval 6.87 to
upper limit of the confidence interval is not yet reached
|
1.18 Months
Interval 0.79 to 4.14
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Overall Survival (OS) is defined as the time from the date of the start of treatment until the date of death. For participants who have not died, OS will be censored at the recorded last date of participant contact, and participants with a missing recorded last date of contact will be censored at the last date the participant was known to be alive.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Overall Survival (OS)
|
45.80 Months
Interval 45.8 to
upper limit of the confidence interval is not yet reached
|
8.77 Months
Interval 1.77 to
upper limit of the confidence interval is not yet reached
|
SECONDARY outcome
Timeframe: From first dose to 30 days post last dose (Up to 66 months)Population: All treated participants
Number of participants with any grade of adverse events (AEs) and any grade of serious adverse events (SAEs) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Adverse Events (AEs)
|
98 Participants
|
18 Participants
|
|
Number of Participants With Adverse Events (AEs)
Serious Adverse Events (SAEs)
|
44 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Up to 66 monthsPopulation: All treated participants
Number of participants who died due to any cause.
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Number of Participants Deaths
|
29 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: From first dose to 30 days post last dose (Up to 66 months)Population: All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter
Number of participants with laboratory abnormalities in specific liver tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN
Outcome measures
| Measure |
Cohort A
n=96 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=15 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
ALT OR AST > 3XULN
|
25 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
ALT OR AST > 5XULN
|
16 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
ALT OR AST > 10XULN
|
7 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
ALT OR AST > 20XULN
|
2 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
TOTAL BILIRUBIN > 2XULN
|
3 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From first dose to 30 days post last dose (Up to 66 months)Population: All treated participants with at least one on-treatment TSH measurement
Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units to determine the safety and tolerability of Nivolumab and Daratumumab. The number of subjects with the following laboratory abnormalities from on-treatment evaluations will be summarized: * TSH value \> ULN and * with baseline TSH value \<= ULN * with at least one FT3/FT4 test value \< LLN within 2-week window after the abnormal TSH test * with all FT3/FT4 test values \>= LLN within 2-week window after the abnormal TSH test * with FT3/FT4 missing within 2-week window after the abnormal TSH test. * TSH \< LLN and * with baseline TSH value \>= LLN * with at least one FT3/FT4 test value \> ULN within 2-week window after the abnormal TSH test * with all FT3/FT4 test values \<= ULN within 2-week window after the abnormal TSH test * with FT3/FT4 missing within 2-week window after the abnormal TSH test
Outcome measures
| Measure |
Cohort A
n=101 Participants
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 Participants
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH > ULN
|
33 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH > ULN WITH TSH <= ULN AT BASELINE
|
26 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN
|
10 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN
|
4 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH > ULN WITH FT3/FT4 TEST MISSING
|
23 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH < LLN
|
38 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH < LLN WITH TSH >= LLN AT BASELINE
|
37 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN
|
7 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN
|
2 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
TSH < LLN WITH FT3/FT4 TEST MISSING
|
15 Participants
|
2 Participants
|
Adverse Events
Cohort A
Serious events: 50 serious events
Other events: 97 other events
Deaths: 29 deaths
Cohort B
Serious events: 14 serious events
Other events: 18 other events
Deaths: 10 deaths
Serious adverse events
| Measure |
Cohort A
n=101 participants at risk
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 participants at risk
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Blood and lymphatic system disorders
WARM TYPE HAEMOLYTIC ANAEMIA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Cardiac disorders
ACUTE CORONARY SYNDROME
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Cardiac disorders
MYOCARDITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
ADRENAL INSUFFICIENCY
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
HYPERTHYROIDISM
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
HYPOPHYSITIS
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
VISION BLURRED
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
COLITIS
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
DIARRHOEA
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
DUODENITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
GASTRITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
IMMUNE-MEDIATED PANCREATITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
NAUSEA
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
SMALL INTESTINAL OBSTRUCTION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
STOMATITIS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
VOMITING
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
DEATH
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
FATIGUE
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
MUCOSAL INFLAMMATION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
OEDEMA PERIPHERAL
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
PYREXIA
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Hepatobiliary disorders
HEPATITIS ACUTE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Immune system disorders
CYTOKINE RELEASE SYNDROME
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
BACILLUS INFECTION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
CELLULITIS ORBITAL
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
CLOSTRIDIUM DIFFICILE INFECTION
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
MENINGITIS BACTERIAL
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
ORBITAL INFECTION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
PNEUMONIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
RASH PUSTULAR
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
SEPSIS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
SEPTIC SHOCK
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
SKIN INFECTION
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
SOFT TISSUE INFECTION
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
STAPHYLOCOCCAL SEPSIS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Injury, poisoning and procedural complications
SYNOVIAL RUPTURE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
AMYLASE INCREASED
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
LIPASE INCREASED
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
TYPE 1 DIABETES MELLITUS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
MYOSITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
RHABDOMYOLYSIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
INTRACRANIAL TUMOUR HAEMORRHAGE
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
50.0%
9/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PSEUDOPROGRESSION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
BRAIN OEDEMA
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
CEREBRAL HAEMORRHAGE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
DYSAESTHESIA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
HAEMORRHAGE INTRACRANIAL
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
HEADACHE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
HEMIPARESIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
ISCHAEMIC STROKE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
LACUNAR INFARCTION
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
METABOLIC ENCEPHALOPATHY
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PARAESTHESIA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PARTIAL SEIZURES
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PERIPHERAL MOTOR NEUROPATHY
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PRESYNCOPE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
SEIZURE
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
SYNCOPE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Renal and urinary disorders
IMMUNE-MEDIATED NEPHRITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Renal and urinary disorders
NEPHRITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
GRANULOMATOUS PNEUMONITIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
LUNG DISORDER
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Vascular disorders
EMBOLISM
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Vascular disorders
HYPOTENSION
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
Other adverse events
| Measure |
Cohort A
n=101 participants at risk
Asymptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
Cohort B
n=18 participants at risk
Symptomatic patients treated with Nivolumab IV 1 mg/kg Q3W + Ipilimumab IV 3 mg/kg Q3W for a total of 4 doses of the combination therapy followed by Nivolumab IV 3 mg/kg BID for a maximum of 24 months or until progression or until unacceptable toxicity.
|
|---|---|---|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
14.9%
15/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
APHASIA
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Blood and lymphatic system disorders
ANAEMIA
|
15.8%
16/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Cardiac disorders
SINUS TACHYCARDIA
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Cardiac disorders
TACHYCARDIA
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Ear and labyrinth disorders
EAR PAIN
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Ear and labyrinth disorders
TINNITUS
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
ADRENAL INSUFFICIENCY
|
9.9%
10/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
HYPERTHYROIDISM
|
13.9%
14/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
HYPOGONADISM
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
HYPOPHYSITIS
|
10.9%
11/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
HYPOTHYROIDISM
|
25.7%
26/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Endocrine disorders
THYROIDITIS
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
IRITIS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
OCULAR HYPERAEMIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
PHOTOPHOBIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
PHOTOPSIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
VISION BLURRED
|
13.9%
14/101 • From first dose to 100 days post last dose (Up to 68 months)
|
27.8%
5/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
VISUAL ACUITY REDUCED
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Eye disorders
VISUAL IMPAIRMENT
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
18.8%
19/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
7.9%
8/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
ABDOMINAL TENDERNESS
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
APHTHOUS ULCER
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
ASCITES
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
CONSTIPATION
|
13.9%
14/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
DIARRHOEA
|
50.5%
51/101 • From first dose to 100 days post last dose (Up to 68 months)
|
44.4%
8/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
DRY MOUTH
|
8.9%
9/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
DYSPEPSIA
|
7.9%
8/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
FLATULENCE
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
NAUSEA
|
52.5%
53/101 • From first dose to 100 days post last dose (Up to 68 months)
|
55.6%
10/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
ORAL DISORDER
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Vascular disorders
HYPOTENSION
|
8.9%
9/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
STOMATITIS
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Gastrointestinal disorders
VOMITING
|
27.7%
28/101 • From first dose to 100 days post last dose (Up to 68 months)
|
33.3%
6/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
ASTHENIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
CHILLS
|
14.9%
15/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
DISEASE PROGRESSION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
FATIGUE
|
68.3%
69/101 • From first dose to 100 days post last dose (Up to 68 months)
|
44.4%
8/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
GAIT DISTURBANCE
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
12.9%
13/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
LOCALISED OEDEMA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
MALAISE
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
OEDEMA
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
OEDEMA PERIPHERAL
|
17.8%
18/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
PAIN
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
General disorders
PYREXIA
|
27.7%
28/101 • From first dose to 100 days post last dose (Up to 68 months)
|
22.2%
4/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Immune system disorders
CYTOKINE RELEASE SYNDROME
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Immune system disorders
HYPERSENSITIVITY
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
CRYPTOCOCCAL FUNGAEMIA
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
IMPETIGO
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
ORAL CANDIDIASIS
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
SINUSITIS
|
7.9%
8/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
TINEA CRURIS
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
10.9%
11/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Infections and infestations
URINARY TRACT INFECTION
|
7.9%
8/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Injury, poisoning and procedural complications
ESCHAR
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Injury, poisoning and procedural complications
FALL
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Injury, poisoning and procedural complications
PROCEDURAL PAIN
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
40.6%
41/101 • From first dose to 100 days post last dose (Up to 68 months)
|
33.3%
6/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
AMYLASE INCREASED
|
16.8%
17/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
38.6%
39/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
|
11.9%
12/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
BLOOD CREATININE INCREASED
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
LIPASE INCREASED
|
24.8%
25/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
LIVER FUNCTION TEST INCREASED
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
LYMPHOCYTE COUNT DECREASED
|
7.9%
8/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
PLATELET COUNT DECREASED
|
8.9%
9/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
WEIGHT DECREASED
|
14.9%
15/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
WEIGHT INCREASED
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
29.7%
30/101 • From first dose to 100 days post last dose (Up to 68 months)
|
22.2%
4/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
10.9%
11/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
10.9%
11/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
8.9%
9/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPOGLYCAEMIA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
8.9%
9/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
13.9%
14/101 • From first dose to 100 days post last dose (Up to 68 months)
|
22.2%
4/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Metabolism and nutrition disorders
HYPOPHOSPHATAEMIA
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
35.6%
36/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
18.8%
19/101 • From first dose to 100 days post last dose (Up to 68 months)
|
22.2%
4/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
GROIN PAIN
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
10.9%
11/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
16.8%
17/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
10.9%
11/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Musculoskeletal and connective tissue disorders
PAIN IN JAW
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PSEUDOPROGRESSION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
AMNESIA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
ATAXIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
BALANCE DISORDER
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
COORDINATION ABNORMAL
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
DIZZINESS
|
17.8%
18/101 • From first dose to 100 days post last dose (Up to 68 months)
|
22.2%
4/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
DYSARTHRIA
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
DYSGEUSIA
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
HAEMORRHAGE INTRACRANIAL
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
HEADACHE
|
51.5%
52/101 • From first dose to 100 days post last dose (Up to 68 months)
|
44.4%
8/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
HYPOAESTHESIA
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
LETHARGY
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
MEMORY IMPAIRMENT
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PARAESTHESIA
|
10.9%
11/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PAROSMIA
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PERIPHERAL MOTOR NEUROPATHY
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
PRESYNCOPE
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
SEIZURE
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Nervous system disorders
SYNCOPE
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Psychiatric disorders
ANXIETY
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Psychiatric disorders
DEPRESSION
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Psychiatric disorders
INSOMNIA
|
22.8%
23/101 • From first dose to 100 days post last dose (Up to 68 months)
|
27.8%
5/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Renal and urinary disorders
NEPHRITIS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Renal and urinary disorders
NOCTURIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Renal and urinary disorders
URINARY RETENTION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Reproductive system and breast disorders
VULVOVAGINAL DRYNESS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
32.7%
33/101 • From first dose to 100 days post last dose (Up to 68 months)
|
33.3%
6/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
DYSPHONIA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
16.8%
17/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
INCREASED BRONCHIAL SECRETION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
14.9%
15/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
8.9%
9/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
TACHYPNOEA
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Respiratory, thoracic and mediastinal disorders
WHEEZING
|
2.0%
2/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
4.0%
4/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
DERMATITIS ACNEIFORM
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
9.9%
10/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
MACULE
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
5.9%
6/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
ONYCHOMADESIS
|
0.00%
0/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
PHOTOSENSITIVITY REACTION
|
0.99%
1/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
41.6%
42/101 • From first dose to 100 days post last dose (Up to 68 months)
|
22.2%
4/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
RASH
|
13.9%
14/101 • From first dose to 100 days post last dose (Up to 68 months)
|
16.7%
3/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
RASH MACULAR
|
3.0%
3/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
41.6%
42/101 • From first dose to 100 days post last dose (Up to 68 months)
|
27.8%
5/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
RASH PRURITIC
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
11.1%
2/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
SKIN HYPOPIGMENTATION
|
9.9%
10/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Skin and subcutaneous tissue disorders
VITILIGO
|
6.9%
7/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Vascular disorders
HOT FLUSH
|
5.0%
5/101 • From first dose to 100 days post last dose (Up to 68 months)
|
5.6%
1/18 • From first dose to 100 days post last dose (Up to 68 months)
|
|
Vascular disorders
HYPERTENSION
|
12.9%
13/101 • From first dose to 100 days post last dose (Up to 68 months)
|
0.00%
0/18 • From first dose to 100 days post last dose (Up to 68 months)
|
Additional Information
Bristol-Myers Squibb Study Director
Bristol-Myers Squibb
Phone: Please Email:
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER