A Study of Nivolumab Combined With Ipilimumab and Nivolumab Alone in Patients With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)
CompletedPhase 2Results postedLast updated 28 August 2024
What this trial tests
Phase 2 trial testing Nivolumab in Pan Tumor in 212 participants. Completed in 2 August 2023.
12 and older, any sex, with Pan Tumor. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm APrimary· From date of randomization up to 42 months
ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on Blinded Independent Central Review (BICR) assessment.
RECIST Criteria:
CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.
PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
RANO Criteria:
CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off cortic
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
22.5
13.9 – 33.2
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
38.6
28.4 – 49.6
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm BSecondary· From date of randomization up to 57 months
ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on Blinded Independent Central Review (BICR) assessment.
RECIST Criteria:
CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.
PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
RANO Criteria:
CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off cortic
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm B: Nivolumab
15.6
6.5 – 29.5
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm B: Nivolumab
29.8
17.3 – 44.9
Objective Response Rate (ORR) Per InvestigatorSecondary· From date of randomization up to 57 months
ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on investigator assessment. Calculated using Clopper-Pearson method.
RECIST Criteria:
CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.
PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
RANO Criteria:
CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
25.0
16.0 – 35.9
Arm B: Nivolumab
13.3
5.1 – 26.8
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
44.3
33.7 – 55.3
Arm B: Nivolumab
23.4
12.3 – 38.0
Duration of Response (DoR) Per InvestigatorSecondary· From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
DoR was defined as the time from first confirmed complete or partial response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Calculated using KM method.
RECIST Criteria:
CR= Disappearance of all target lesions. PR= ≥ 30% decrease in the sum of diameters of target lesions. PD= ≥ 20% increase in the sum of diameters of target lesions.
RANO Criteria:
CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable/improved T2/FLAIR; off corticosteroids; stable/improved clinically PR= ≥ 50% decrease in the sum of diamete
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
27.96
11.20 – NA
Arm B: Nivolumab
NA
11.24 – NA
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
NA
27.96 – NA
Arm B: Nivolumab
NA
8.05 – NA
Duration of Response (DoR) Per Blinded Independent Central Review (BICR)Secondary· From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
DoR was defined as the time from first confirmed complete or partial response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Calculated using KM method.
RECIST Criteria:
CR= Disappearance of all target lesions. PR= ≥ 30% decrease in the sum of diameters of target lesions. PD= ≥ 20% increase in the sum of diameters of target lesions.
RANO Criteria:
CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable/improved T2/FLAIR; off corticosteroids; stable/improved clinically PR= ≥ 50% decrease in the sum of diamete
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
NA
10.15 – NA
Arm B: Nivolumab
NA
5.52 – NA
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
NA
33.51 – NA
Arm B: Nivolumab
NA
8.31 – NA
Time to Objective Response (TTR) Per InvestigatorSecondary· From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months)
TTR is defined as the time from randomization date to the date of the first confirmed response (complete response (CR) or partial response (PR)), based on investigator assessment.
RECIST Criteria:
CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.
PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
RANO Criteria:
CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable o
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
3.48
± 1.17
Arm B: Nivolumab
4.08
± 3.40
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
3.56
± 1.74
Arm B: Nivolumab
3.75
± 2.50
Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)Secondary· From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months)
TTR is defined as the time from randomization date to the date of the first confirmed response (complete response (CR) or partial response (PR)), based on Blinded Independent Central Review (BICR) assessment.
RECIST Criteria:
CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm.
PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
RANO Criteria:
CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
3.59
± 1.65
Arm B: Nivolumab
4.33
± 2.93
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
4.37
± 5.10
Arm B: Nivolumab
3.98
± 2.47
Clinical Benefit Rate (CBR) Per InvestigatorSecondary· From date of randomization up to 57 months
CBR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD) based on investigator assessment.
RECIST Criteria:
CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm PR= ≥ 30% decrease in the sum of diameters of target lesions SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
RANO Criteria:
CR= Disappearance of all enhancing disease; stable or improved nonenhancing T2/FLAIR lesions; off
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
42.5
31.5 – 54.1
Arm B: Nivolumab
40.0
25.7 – 55.7
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
63.6
52.7 – 73.6
Arm B: Nivolumab
46.8
32.1 – 61.9
Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)Secondary· From date of randomization up to 57 months
CBR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD) per Blinded Independent Central Review (BICR) assessment.
RECIST Criteria:
CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm PR= ≥ 30% decrease in the sum of diameters of target lesions SD= does not qualify for PR or progressive disease
RANO Criteria:
CR= Disappearance of all enhancing disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; a
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
32.5
22.4 – 43.9
Arm B: Nivolumab
28.9
16.4 – 44.3
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
53.4
42.5 – 64.1
Arm B: Nivolumab
38.3
24.5 – 53.6
Progression Free Survival (PFS) Per InvestigatorSecondary· From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
PFS is defined as the time from randomization date to the date of the first documented tumor progression, determined by investigator assessment, or death due to any cause, whichever occurs first. Calculated using KM method.
RECIST Criteria:
Progressive Disease (PD)= ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm.
RANO Criteria:
PD= ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
2.99
2.66 – 4.34
Arm B: Nivolumab
3.04
2.79 – 5.36
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
8.15
4.83 – 12.94
Arm B: Nivolumab
3.06
2.79 – 10.91
Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)Secondary· From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)
PFS is defined as the time from randomization date to the date of the first documented tumor progression, determined by Blinded Independent Central Review (BICR) assessment, or death due to any cause, whichever occurs first. Calculated using KM method.
RECIST Criteria:
Progressive Disease (PD)= ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm.
RANO Criteria:
PD= ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with t
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
2.83
2.33 – 2.99
Arm B: Nivolumab
2.83
2.60 – 3.25
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
5.68
3.19 – 11.60
Arm B: Nivolumab
2.83
2.69 – 5.72
Overall Survival (OS)Secondary· From date of randomization to date of death (Up to 57 months)
OS is defined as the time between the date of randomization and the date of death due to any cause. Participants who did not have a date of death were censored on the last date for which a participant was known to be alive. Calculated using KM method.
Blood TMB-H (bTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
8.07
5.82 – 10.45
Arm B: Nivolumab
11.24
5.26 – 18.99
Tissue TMB-H (tTMB-H)
Group
Value
95% CI
Arm A: Nivolumab+Ipilimumab
16.48
10.18 – 30.52
Arm B: Nivolumab
14.59
7.69 – 18.23
Adverse events — posted to ClinicalTrials.gov
Time frame: SAEs and AEs are assessed from first dose to 100 days post last dose (Up to 27 months). Participants were assessed for all-cause mortality from their first dose to study completion (Up to 57 months)..
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Arm A: Nivolumab+Ipilimumab
Serious: 90/135 (67%)
Deaths: 97/136
Arm B: Nivolumab
Serious: 39/76 (51%)
Deaths: 42/76
Arm B: Nivolumab+Ipilimumab (Rollover)
Serious: 11/22 (50%)
Deaths: 20/22
Serious adverse events (102 terms)
Reaction
System
Arm A: Nivolumab+Ipilimumab
Arm B: Nivolumab
Arm B: Nivolumab+Ipilimuma…
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
The purpose of this study is to demonstrate the clinical activity of nivolumab in combination with ipilimumab in multiple types of tumors based on their Tumor Mutational Burden status.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
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Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Bristol-Myers Squibb
Last refreshed: 28 August 2024
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03668119.