Cancer, Hepatocellular
Conditions
Brief summary
The purpose of this study is to evaluate the safety and tolerability of nivolumab with and without ipilimumab in combination with Trans-arterial ChemoEmbolization (TACE) to TACE alone in participants with intermediate liver cancer.
Interventions
DRUGnivolumab
Specified dose on specified days
DRUGipilimumab
Specified dose on specified days
PROCEDURETACE
TACE (Trans-arterial ChemoEmbolization)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has intermediate-stage hepatocellular carcinoma (HCC) whose tumor characteristics exceed the Beyond Milan and Up-to-7 (BMU7) criteria and is eligible for trans-arterial ChemoEmbolization (TACE) * Participant has no extrahepatic spreading (EHS), no regional lymph node involvement, no main, left main, or right main portal vein thrombosis, and no macrovascular invasion (MVI) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Exclusion criteria
* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC * Prior liver transplant or participants who are on the waiting list for liver transplantation * Active, known, or suspected autoimmune disease Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose and 30 days after last dose of study therapy (up to approximately 25 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| Number of Participants With Serious Adverse Events (SAEs) | From first dose and 30 days after last dose of study therapy (up to approximately 25 months) | Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose that results in death, Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) or requires inpatient hospitalization or causes prolongation of existing hospitalization, or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event. |
| Number of Participants Who Died | From first dose and 100 days after last dose of study therapy (up to approximately 27 months) | Number of participants who died due to any cause are summarized. |
| Number of Participants With Adverse Events Leading to Study Drug Discontinuation | From first dose and 30 days after last dose of study therapy (up to approximately 25 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | From first dose and 30 days after last dose of study therapy (up to approximately 25 months) | Laboratory results were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 =Severe, Grade 4 = Life-threatening). Highest grade measured for hemoglobin and albumin was Grade 3. |
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | From first dose and 30 days after last dose of study therapy (up to approximately 25 months) | Blood samples were collected for specific thyroid test. |
| Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | From first dose and 30 days after last dose of study therapy (up to approximately 25 months) | Blood samples were collected for specific liver tests. |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, France, Germany, Hong Kong, Italy, Japan, Poland, Puerto Rico, Russia, Singapore, South Korea, Spain, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NIVO+IPI+TACE Participants with intermediate-stage hepatocellular carcinoma (HCC) received Nivolumab (NIVO) 240 milligram (mg) every 2 weeks (Q2W) and ipilimumab (IPI) 1 milligram per kilogram (mg/kg) every 6 weeks (Q6W) as an approximately 30-minute infusion. Participants received first Trans-arterial ChemoEmbolization (TACE) in 7 days after randomization and then TACE as needed, until participant was no longer eligible for further TACE, unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first. | 9 |
| NIVO+TACE Participants with intermediate-stage hepatocellular carcinoma (HCC) received Nivolumab 240 milligram (mg) every 2 weeks (Q2W) as an approximately 30-minute infusion. Participants received first Trans-arterial ChemoEmbolization (TACE) in 7 days after randomization and then TACE as needed, until participant was no longer eligible for further TACE, unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first. Per Protocol Amendment 01, participants did not receive placebo infusions following unblinding. | 9 |
| TACE Participants received first Trans-arterial ChemoEmbolization (TACE) in 7 days after randomization and then TACE as needed, until participant was no longer eligible for further TACE, unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first. Per Protocol Amendment 01, participants did not receive placebo infusions following unblinding. | 8 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative reasons by sponsor | 0 | 1 | 0 |
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Disease progression | 1 | 2 | 3 |
| Overall Study | Disease recurrence | 0 | 1 | 0 |
| Overall Study | Other reason | 0 | 0 | 1 |
| Overall Study | Study drug toxicity | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | TACE | NIVO+TACE | NIVO+IPI+TACE |
|---|---|---|---|---|
| Age, Continuous | 68.3 years STANDARD_DEVIATION 10.7 | 70.3 years STANDARD_DEVIATION 8.89 | 62.7 years STANDARD_DEVIATION 11.19 | 72.3 years STANDARD_DEVIATION 10.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 4 Participants | 4 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants | 4 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 4 participants | 3 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Chinese | 5 participants | 1 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Japanese | 5 participants | 2 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Not Reported | 3 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White | 8 participants | 2 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 22 Participants | 7 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 9 | 2 / 9 | 0 / 8 |
| other Total, other adverse events | 9 / 9 | 9 / 9 | 8 / 8 |
| serious Total, serious adverse events | 7 / 9 | 6 / 9 | 2 / 8 |
Outcome results
Primary
Number of Participants Who Died
Number of participants who died due to any cause are summarized.
Time frame: From first dose and 100 days after last dose of study therapy (up to approximately 27 months)
Population: All treated participants included all enrolled participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NIVO+IPI+TACE | Number of Participants Who Died | 2 Participants |
| NIVO+TACE | Number of Participants Who Died | 2 Participants |
| TACE | Number of Participants Who Died | 0 Participants |
Primary
Number of Participants With Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Population: All treated participants included all enrolled participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NIVO+IPI+TACE | Number of Participants With Adverse Events | 9 Participants |
| NIVO+TACE | Number of Participants With Adverse Events | 9 Participants |
| TACE | Number of Participants With Adverse Events | 8 Participants |
Primary
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Population: All treated participants included all enrolled participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NIVO+IPI+TACE | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 3 Participants |
| NIVO+TACE | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 1 Participants |
| TACE | Number of Participants With Adverse Events Leading to Study Drug Discontinuation | 1 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests
Blood samples were collected for specific liver tests.
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Population: All treated participants included all enrolled participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NIVO+IPI+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Alanine Transaminase (ALT) or AST > 10 X ULN | 2 Participants |
| NIVO+IPI+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALP (Alkaline Phosphatase) > 1.5 X ULN | 5 Participants |
| NIVO+IPI+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Total Bilirubin > 2 X ULN | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5 X Upper limit of Normal (ULN) | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3 X ULN with total Bilirubin > 2 X ULN within 30 days | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT OR AST Elevation > 3 X ULN with total Bilirubin > 2 X ULN within one day | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALT or Aspartate Transaminase (AST) > 20 X ULN | 1 Participants |
| NIVO+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Total Bilirubin > 2 X ULN | 2 Participants |
| NIVO+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5 X Upper limit of Normal (ULN) | 2 Participants |
| NIVO+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Alanine Transaminase (ALT) or AST > 10 X ULN | 1 Participants |
| NIVO+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALT or Aspartate Transaminase (AST) > 20 X ULN | 0 Participants |
| NIVO+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALP (Alkaline Phosphatase) > 1.5 X ULN | 5 Participants |
| NIVO+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT OR AST Elevation > 3 X ULN with total Bilirubin > 2 X ULN within one day | 1 Participants |
| NIVO+TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3 X ULN with total Bilirubin > 2 X ULN within 30 days | 2 Participants |
| TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALP (Alkaline Phosphatase) > 1.5 X ULN | 5 Participants |
| TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Alanine Transaminase (ALT) or AST > 10 X ULN | 0 Participants |
| TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3 X ULN with total Bilirubin > 2 X ULN within 30 days | 0 Participants |
| TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT OR AST Elevation > 3 X ULN with total Bilirubin > 2 X ULN within one day | 0 Participants |
| TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | Total Bilirubin > 2 X ULN | 1 Participants |
| TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALT or Aspartate Transaminase (AST) > 20 X ULN | 0 Participants |
| TACE | Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5 X Upper limit of Normal (ULN) | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
Blood samples were collected for specific thyroid test.
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Population: All treated participants with at least one on-treatment thyroid stimulating hormone (TSH) measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN (Upper Limit of Normal) | 5 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with TSH <= ULN at baseline | 5 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with at least one FT3/FT4 test value < LLN (Lower Limit of Normal) | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with all other FT3/FT4 test values >= LLN | 5 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with FT3/FT4 test missing | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with TSH >= LLN at baseline | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with at least one FT3/FT4 test value > ULN | 2 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | With all other FT3/FT4 test values <= ULN | 3 Participants |
| NIVO+IPI+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | With FT3/FT4 test missing | 0 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | With all other FT3/FT4 test values <= ULN | 0 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN (Upper Limit of Normal) | 5 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 1 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with FT3/FT4 test missing | 2 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with TSH <= ULN at baseline | 4 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | With FT3/FT4 test missing | 1 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with at least one FT3/FT4 test value > ULN | 0 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with at least one FT3/FT4 test value < LLN (Lower Limit of Normal) | 1 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with TSH >= LLN at baseline | 1 Participants |
| NIVO+TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with all other FT3/FT4 test values >= LLN | 4 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with at least one FT3/FT4 test value > ULN | 0 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with all other FT3/FT4 test values >= LLN | 4 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with FT3/FT4 test missing | 1 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 0 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | With all other FT3/FT4 test values <= ULN | 0 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with TSH >= LLN at baseline | 0 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN (Upper Limit of Normal) | 5 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | With FT3/FT4 test missing | 0 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with TSH <= ULN at baseline | 3 Participants |
| TACE | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with at least one FT3/FT4 test value < LLN (Lower Limit of Normal) | 3 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs)
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose that results in death, Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) or requires inpatient hospitalization or causes prolongation of existing hospitalization, or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event.
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Population: All treated participants included all enrolled participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NIVO+IPI+TACE | Number of Participants With Serious Adverse Events (SAEs) | 7 Participants |
| NIVO+TACE | Number of Participants With Serious Adverse Events (SAEs) | 6 Participants |
| TACE | Number of Participants With Serious Adverse Events (SAEs) | 2 Participants |
Primary
Number of Participants With Worst Grade (Grade 3/4) Laboratory Results
Laboratory results were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 =Severe, Grade 4 = Life-threatening). Highest grade measured for hemoglobin and albumin was Grade 3.
Time frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Population: All treated participants included all enrolled participants who received at least one dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Bilirubin, TOTAL (Grade 4) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Platelet count (Grade 3) | 2 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Platelet Count (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Leukocytes (Grade 3) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Leukocytes (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lymphocytes (Grade 3) | 2 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lymphocytes (Grade 4) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Aspartate Aminotransferase (Grade 3) | 2 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Aspartate Aminotransferase (Grade 4) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alanine Aminotransferase (Grade 3) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alanine Aminotransferase (Grade 4) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Bilirubin, Total (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hemoglobin (Grade 3) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Creatinine, (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Creatinine (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Potassium, (Grade 3) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Potassium (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Amylase (Grade 3) | 2 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Amylase (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lipase (Grade 3) | 4 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lipase (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Albumin, (Grade 3) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Absolute Neutrophil Count (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Absolute Neutrophil Count (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alkaline Phosphatase (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alkaline Phosphatase (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Sodium (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Sodium (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Calcium, Total (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Calcium, Total (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Magnesium (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Magnesium (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Glucose (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Glucose (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypernatremia (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypernatremia (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyponatremia (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyponatremia (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyperkalemia (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyperkalemia (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypokalemia (Grade 3) | 1 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypokalemia (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypercalcemia (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypercalcemia (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypermagnesemia (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypermagnesemia (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypomagnesemia (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypomagnesemia (Grade 4) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypoglycemia (Grade 3) | 0 Participants |
| NIVO+IPI+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypoglycemia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Potassium (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypomagnesemia (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Amylase (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyperkalemia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Amylase (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lipase (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lipase (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypokalemia (Grade 3) | 1 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Albumin, (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Absolute Neutrophil Count (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Absolute Neutrophil Count (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypokalemia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alkaline Phosphatase (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alkaline Phosphatase (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypomagnesemia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Sodium (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypercalcemia (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Sodium (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Calcium, Total (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Calcium, Total (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypercalcemia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Magnesium (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Magnesium (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypoglycemia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Glucose (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypermagnesemia (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Glucose (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hemoglobin (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Platelet count (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Platelet Count (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypernatremia (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Leukocytes (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Leukocytes (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypoglycemia (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lymphocytes (Grade 3) | 2 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypernatremia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lymphocytes (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Aspartate Aminotransferase (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypermagnesemia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Aspartate Aminotransferase (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyponatremia (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alanine Aminotransferase (Grade 3) | 1 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alanine Aminotransferase (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Bilirubin, Total (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyponatremia (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Bilirubin, TOTAL (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Creatinine, (Grade 3) | 1 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Creatinine (Grade 4) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyperkalemia (Grade 3) | 0 Participants |
| NIVO+TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Potassium, (Grade 3) | 1 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Aspartate Aminotransferase (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Potassium (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hemoglobin (Grade 3) | 2 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Amylase (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Glucose (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Creatinine, (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Amylase (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyperkalemia (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Platelet count (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lipase (Grade 3) | 1 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypomagnesemia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypermagnesemia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lipase (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alanine Aminotransferase (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Platelet Count (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Albumin, (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypokalemia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyponatremia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Absolute Neutrophil Count (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypoglycemia (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypoglycemia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Absolute Neutrophil Count (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Leukocytes (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypernatremia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alkaline Phosphatase (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypokalemia (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alanine Aminotransferase (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Alkaline Phosphatase (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Leukocytes (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypermagnesemia (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Sodium (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Potassium, (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lymphocytes (Grade 3) | 3 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Sodium (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypercalcemia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Bilirubin, Total (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Calcium, Total (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypomagnesemia (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Creatinine (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Calcium, Total (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Lymphocytes (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypernatremia (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Magnesium (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hypercalcemia (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyperkalemia (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Magnesium (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Aspartate Aminotransferase (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Bilirubin, TOTAL (Grade 4) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Glucose (Grade 3) | 0 Participants |
| TACE | Number of Participants With Worst Grade (Grade 3/4) Laboratory Results | Hyponatremia (Grade 4) | 0 Participants |