Trial Outcomes & Findings for Safety and Bioactivity of Ipilimumab and Nivolumab Combination Prior to Liver Resection in Hepatocellular Carcinoma (NCT NCT03682276)
NCT ID: NCT03682276
Last Updated: 2026-06-29
Results Overview
Number of patients with an unplanned delay to surgery to Day 89 or later
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
33 participants
Primary outcome timeframe
Up to Day 89
Results posted on
2026-06-29
Participant Flow
Participant milestones
| Measure |
Treatment Group
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Overall Study
STARTED
|
33
|
|
Overall Study
COMPLETED
|
33
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Bioactivity of Ipilimumab and Nivolumab Combination Prior to Liver Resection in Hepatocellular Carcinoma
Baseline characteristics by cohort
| Measure |
Treatment Group
n=33 Participants
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Age, Continuous
|
68 years
n=9 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=9 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Asian
|
7 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
White
|
22 Participants
n=9 Participants
|
|
Race/Ethnicity, Customized
Other Ethnic Group
|
1 Participants
n=9 Participants
|
|
Region of Enrollment
United Kingdom
|
33 participants
n=9 Participants
|
|
Aetiology
Hepatitis B Virus (HBV)
|
4 Participants
n=9 Participants
|
|
Aetiology
Hepatitis C Virus (HCV)
|
8 Participants
n=9 Participants
|
|
Aetiology
Alcohol
|
8 Participants
n=9 Participants
|
|
Aetiology
Metabolic dysfunction-Associated Steatotic Liver Disease
|
3 Participants
n=9 Participants
|
|
Aetiology
Cryptogenic
|
9 Participants
n=9 Participants
|
|
Aetiology
Hemochromatosis
|
1 Participants
n=9 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score
Score 0
|
25 Participants
n=9 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score
Score 1
|
8 Participants
n=9 Participants
|
|
Barcelona Clinic Liver Cancer (BCLC) stage
Stage A
|
23 Participants
n=9 Participants
|
|
Barcelona Clinic Liver Cancer (BCLC) stage
Stage B
|
10 Participants
n=9 Participants
|
|
Child-Pugh score
Class A: Score 5
|
28 Participants
n=9 Participants
|
|
Child-Pugh score
Class A: Score 6
|
5 Participants
n=9 Participants
|
PRIMARY outcome
Timeframe: Up to Day 89Population: This is the number of patients who proceeded to receive surgery after receiving the study drug.
Number of patients with an unplanned delay to surgery to Day 89 or later
Outcome measures
| Measure |
Treatment Group
n=30 Participants
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Delay to Surgery
|
2 Participants
|
PRIMARY outcome
Timeframe: Up to Day 127Safety and tolerability of the nivolumab and ipilimumab combination based on NCI CTCAE v5.0 criteria from the day of first nivolumab and ipilimumab administration to 126 days later. Treatment-related adverse events (TRAE) are defined as any unfavorable medical occurrence, symptom, or abnormal laboratory finding in a participant that is deemed to be either definitely, probably, or possibly caused by the trial treatment.
Outcome measures
| Measure |
Treatment Group
n=33 Participants
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Frequency of Treatment-related Adverse Events [Safety and Tolerability]
|
25 Participants
|
SECONDARY outcome
Timeframe: Up to Day 43Population: One trial participant was found to have cholangiocarcinoma (CCA) following liver resection specimen collection and was excluded from the efficacy analysis population.
Objective response rate (complete or partial response) on pre-resection imaging 42 days after the day of first nivolumab and ipilimumab administration using Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. The criteria classifies response based on the assessment of target and non-target lesions on scans as: Complete Response (CR): requires all of: * disappearance of all target and non-target lesions * pathological lymph nodes must have reduced to \<10 mm in short axis * no new lesions Partial Response (PR): requires all of: * at least 30% decrease in sum of diameters (SOD) of target lesions compared to baseline sum diameters * non-progressive disease of non-target lesions * no new lesions Progressive Disease (PD): either one of: * any new lesions * at least 20% relative and 5 mm absolute increase of SOD of target lesions compared to smallest SOD ever recorded for the patient Stable Disease (SD): not meeting criteria for PD or PR.
Outcome measures
| Measure |
Treatment Group
n=32 Participants
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Objective Response Rate
|
8 Participants
|
SECONDARY outcome
Timeframe: Up to Day 88 or up to liver resection, whichever came firstPopulation: The number of participants evaluable for measuring pathological response.
Pathologic response rate (≥70%) on hematoxylin and eosin evaluation of the resected specimen.
Outcome measures
| Measure |
Treatment Group
n=27 Participants
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Pathologic Response Rate
|
9 Participants
|
Adverse Events
Treatment Group
Serious events: 3 serious events
Other events: 28 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Treatment Group
n=33 participants at risk
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Hepatobiliary disorders
Hepatic decompensation
|
3.0%
1/33 • Number of events 1 • Up to Day 127 from date of study enrollment.
|
|
Investigations
Hyperglycaemia
|
3.0%
1/33 • Number of events 1 • Up to Day 127 from date of study enrollment.
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of breath
|
3.0%
1/33 • Number of events 1 • Up to Day 127 from date of study enrollment.
|
|
Immune system disorders
Immune-mediated myocarditis
|
3.0%
1/33 • Number of events 1 • Up to Day 127 from date of study enrollment.
|
Other adverse events
| Measure |
Treatment Group
n=33 participants at risk
Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks
Ipilimumab: Ipilimumab is a monoclonal antibody given as an immunotherapy
Nivolumab: Nivolumab is a monoclonal antibody given as an immunotherapy
|
|---|---|
|
Hepatobiliary disorders
Hepatic function abnormal
|
42.4%
14/33 • Number of events 26 • Up to Day 127 from date of study enrollment.
|
|
General disorders
Fatigue
|
39.4%
13/33 • Number of events 17 • Up to Day 127 from date of study enrollment.
|
|
Gastrointestinal disorders
Diarrhoea
|
21.2%
7/33 • Number of events 8 • Up to Day 127 from date of study enrollment.
|
|
Investigations
Weight decreased
|
21.2%
7/33 • Number of events 7 • Up to Day 127 from date of study enrollment.
|
|
Gastrointestinal disorders
Abdominal pain
|
18.2%
6/33 • Number of events 6 • Up to Day 127 from date of study enrollment.
|
|
Gastrointestinal disorders
Constipation
|
18.2%
6/33 • Number of events 6 • Up to Day 127 from date of study enrollment.
|
|
Infections and infestations
Urinary tract infection
|
15.2%
5/33 • Number of events 5 • Up to Day 127 from date of study enrollment.
|
|
Endocrine disorders
Hyperthyroidism
|
12.1%
4/33 • Number of events 5 • Up to Day 127 from date of study enrollment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.1%
4/33 • Number of events 5 • Up to Day 127 from date of study enrollment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.2%
5/33 • Number of events 5 • Up to Day 127 from date of study enrollment.
|
|
Blood and lymphatic system disorders
Anaemia
|
9.1%
3/33 • Number of events 4 • Up to Day 127 from date of study enrollment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
12.1%
4/33 • Number of events 4 • Up to Day 127 from date of study enrollment.
|
|
Nervous system disorders
Headache
|
12.1%
4/33 • Number of events 4 • Up to Day 127 from date of study enrollment.
|
|
Hepatobiliary disorders
Hypoalbuminaemia
|
9.1%
3/33 • Number of events 4 • Up to Day 127 from date of study enrollment.
|
|
General disorders
Pain
|
9.1%
3/33 • Number of events 4 • Up to Day 127 from date of study enrollment.
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
3/33 • Number of events 4 • Up to Day 127 from date of study enrollment.
|
|
Investigations
Blood thyroid stimulating hormone decreased
|
9.1%
3/33 • Number of events 3 • Up to Day 127 from date of study enrollment.
|
|
Endocrine disorders
Hypothyroidism
|
9.1%
3/33 • Number of events 3 • Up to Day 127 from date of study enrollment.
|
|
General disorders
Procedural pain
|
9.1%
3/33 • Number of events 3 • Up to Day 127 from date of study enrollment.
|
|
General disorders
Pyrexia
|
9.1%
3/33 • Number of events 3 • Up to Day 127 from date of study enrollment.
|
|
Gastrointestinal disorders
Dysphagia
|
6.1%
2/33 • Number of events 2 • Up to Day 127 from date of study enrollment.
|
|
Infections and infestations
Viral infection
|
6.1%
2/33 • Number of events 2 • Up to Day 127 from date of study enrollment.
|
|
Vascular disorders
Dizziness
|
6.1%
2/33 • Number of events 2 • Up to Day 127 from date of study enrollment.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.1%
2/33 • Number of events 2 • Up to Day 127 from date of study enrollment.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
6.1%
2/33 • Number of events 2 • Up to Day 127 from date of study enrollment.
|
|
General disorders
Temperature intolerance
|
6.1%
2/33 • Number of events 2 • Up to Day 127 from date of study enrollment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place