CClinicalTrials.gg
Sign In
CompletedNCT02905266Updated Dec 17, 2020Results posted

A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma

A Phase 3 interventional study of Nivolumab and Ipilimumab in Melanoma, sponsored by Bristol-Myers Squibb. Completed at 16 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-12-17.

Sponsored by Bristol-Myers Squibb · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
106
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a safety and efficacy study of different administration regimens of nivolumab plus Ipilimumab in subjects with previously untreated, unresectable or metastatic melanoma.

02

Conditions studied

  • Melanoma

Browse trials for

03

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 106 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.

Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion criteria

Inclusion Criteria:

  • Males and Females, ages 15 years ≥ of age (Except where local regulations and/or institutional policies do not allow for subjects \< 18 years of age to participate)
  • Subjects must have been diagnosed with stage III or/and stage IV histologically confirmed melanoma that is unresectable or metastatic
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Subjects have not been treated by systemic anticancer therapy for unresectable or metastatic melanoma

Exclusion criteria

Exclusion Criteria:

  • Subjects with active brain metastases or leptomeningeal metastases
  • Subjects with ocular melanoma
  • Subjects with active, known or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria could apply

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
106 participants (actual)

Study arms

  • Experimental
    Nivolumab and Ipilimumab Concomitant Administration

    Followed by Nivolumab monotherapy

    Biological: Nivolumab · Biological: Ipilimumab

  • Experimental
    Nivolumab and Ipilimumab Sequential Administration

    Followed by Nivolumab monotherapy

    Biological: Nivolumab · Biological: Ipilimumab

Interventions

  • BiologicalNivolumab

    -Specified dose on specified days

  • BiologicalIpilimumab

    -Specified dose on specified days

06

What researchers measure

Primary outcomes

  1. Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)

    This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction broad scope SMQ. Such AEs include any acute systemic reaction characterized by a large list of terms, including (but not limited to) pruritus, urticaria, flushing, hypotension, respiratory distress, and vascular insufficiency. It also includes other signs and symptoms such as asthma, choking sensation, coughing, sneezing, and difficulty breathing due to laryngeal spasm and/or bronchospasm. Less frequent clinical presentations are also captured and include hyperventilation, sensation of foreign body, and ocular edema.

    Time frame: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

Secondary outcomes

  1. Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ

    This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction narrow scope SMQ. The narrow scope SMQ is composed of a large list of terms, including (but not limited to) anaphylactic shock and reaction, shock and shock symptoms, and circulatory collapse, among the others.

    Time frame: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

  2. Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs

    This outcome describes the percentage of participants experiencing at least 1 AE in the Hypersensitivity/Infusion select AEs category. The select AEs consist of a list of preferred terms defined by the Sponsor and represent AEs with a potential immune-mediated etiology. The following 5 MedDRA preferred terms are included in the hypersensitivity/infusion reaction select AE category: Anaphylactic Reaction, Anaphylactic Shock, Bronchospasm, Hypersensitivity, and Infusion Related Reaction

    Time frame: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

  3. Percentage of Participants Affected by All Causality Grade 3 - 5 AEs

    This outcome describes the percentage of participants who experienced at least 1 AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria

    Time frame: From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)

  4. Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs

    This outcome describes the percentage of participants who experienced at least 1 Drug-related AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria

    Time frame: From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)

  5. Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI)

    Time frame: From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported.

  6. Geometric Mean Concentration of Nivolumab at End of Infusion (EOI)

    Time frame: From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported

  7. Geometric Mean Trough Concentration of Ipilimumab

    Time frame: From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.

  8. Geometric Mean Trough Concentration of Nivolumab

    Time frame: From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.

  9. Objective Response Rate (ORR)

    The ORR is defined as the proportion of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.

    Time frame: Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)

  10. Progression Free Survival (PFS)

    PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first.

    Time frame: From the date of randomization to the first date of documented progression (approximately 26 months)

07

Results

Posted Jan 8, 2019

Participant flow

Treatment Phase Part 1
Participant flow — Treatment Phase Part 1
MilestoneFixed Ratio CombinationSequential Combination
Started5353
Completed2430
Not completed2923
Withdrew: Participant withdrew consent10
Withdrew: Disease progression67
Withdrew: Study drug toxicity2216
Transition From Part 1 to Part 2
Participant flow — Transition From Part 1 to Part 2
MilestoneFixed Ratio CombinationSequential Combination
Started2430
Completed2022
Not completed48
Withdrew: Adverse event unrelated to study drug10
Withdrew: Disease progression21
Withdrew: Study drug toxicity04
Withdrew: Death01
Withdrew: Participant withdrew consent01
Withdrew: Adverse event11
Maintenance Phase Part 2
Participant flow — Maintenance Phase Part 2
MilestoneFixed Ratio CombinationSequential Combination
Started2022
Completed814
Not completed128
Withdrew: Disease progression92
Withdrew: Study drug toxicity34
Withdrew: Maximum clinical benefit02

Outcome measures

SecondaryPercentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ

This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction narrow scope SMQ. The narrow scope SMQ is composed of a large list of terms, including (but not limited to) anaphylactic shock and reaction, shock and shock symptoms, and circulatory collapse, among the others.

Time frame:
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Reported as:
Number · Percent of Participants
Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ
Percent of ParticipantsFixed Ratio CombinationSequential Combination
Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ0.0 (0.0 to 6.7)0.0 (0.0 to 6.7)
Statistical analysis
  • Fixed Ratio Combination vs Sequential Combination · Percent difference in incidence rates: 0.0 · 95% CI 0.0 to 0.0Fixed Ratio Combination over Sequential Combination
SecondaryPercentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs

This outcome describes the percentage of participants experiencing at least 1 AE in the Hypersensitivity/Infusion select AEs category. The select AEs consist of a list of preferred terms defined by the Sponsor and represent AEs with a potential immune-mediated etiology. The following 5 MedDRA preferred terms are included in the hypersensitivity/infusion reaction select AE category: Anaphylactic Reaction, Anaphylactic Shock, Bronchospasm, Hypersensitivity, and Infusion Related Reaction

Time frame:
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Reported as:
Number · Percent of Participants
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs
Percent of ParticipantsFixed Ratio CombinationSequential Combination
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs7.59.4
SecondaryPercentage of Participants Affected by All Causality Grade 3 - 5 AEs

This outcome describes the percentage of participants who experienced at least 1 AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria

Time frame:
From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
Reported as:
Number · Percent of participants
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs
Percent of participantsFixed Ratio CombinationSequential Combination
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs69.856.6
SecondaryPercentage of Participants Affected by Drug-related Grade 3 - 5 AEs

This outcome describes the percentage of participants who experienced at least 1 Drug-related AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria

Time frame:
From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
Reported as:
Number · Percent of participants
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs
Percent of participantsFixed Ratio CombinationSequential Combination
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs58.547.2
SecondaryGeometric Mean Concentration of Ipilimumab at End of Infusion (EOI)
Time frame:
From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported.
Reported as:
Geometric mean · micrograms per milliliter (ug/mL)
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI)
micrograms per milliliter (ug/mL)Fixed Ratio CombinationSequential Combination
Cycle 1 Day 160.4 ± 93.061.5 ± 72.3
Cycle 2 Day 166.8 ± 13472.1 ± 71.8
Cycle 4 Day 177.9 ± 94.284.6 ± 104
SecondaryGeometric Mean Concentration of Nivolumab at End of Infusion (EOI)
Time frame:
From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported
Reported as:
Geometric mean · micrograms per milliliter (ug/mL)
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI)
micrograms per milliliter (ug/mL)Fixed Ratio CombinationSequential Combination
Cycle 1 Day 120.9 ± 77.321.8 ± 117
Cycle 2 Day 124.2 ± 12222.4 ± 101
Cycle 4 Day 127.9 ± 79.827.4 ± 79.9
SecondaryGeometric Mean Trough Concentration of Ipilimumab
Time frame:
From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Reported as:
Geometric mean · micrograms per milliliter (ug/mL)
Geometric Mean Trough Concentration of Ipilimumab
micrograms per milliliter (ug/mL)Fixed Ratio CombinationSequential Combination
Cycle 2 Day 110.8 ± 30.29.94 ± 38.9
Cycle 4 Day 116.5 ± 36.913.7 ± 46.0
SecondaryGeometric Mean Trough Concentration of Nivolumab
Time frame:
From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Reported as:
Geometric mean · micrograms per milliliter (ug/mL)
Geometric Mean Trough Concentration of Nivolumab
micrograms per milliliter (ug/mL)Fixed Ratio CombinationSequential Combination
Cycle 2 Day 13.94 ± 56.62.75 ± 65.9
Cycle 4 Day 16.50 ± 44.64.05 ± 75.3
SecondaryObjective Response Rate (ORR)

The ORR is defined as the proportion of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.

Time frame:
Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)
Reported as:
Number · Percentage of Participants
Objective Response Rate (ORR)
Percentage of ParticipantsFixed Ratio CombinationSequential Combination
Objective Response Rate (ORR)52.8 (38.6 to 66.7)60.4 (46.0 to 73.5)
Statistical analysis
  • Fixed Ratio Combination vs Sequential Combination · Percent difference of orrs: -7.5 · 95% CI -26.1 to 11.0Cochran-Mantel-Haenszel (CMH) method of weighting
  • Fixed Ratio Combination vs Sequential Combination · Odds ratio (or): 0.75 · 95% CI 0.35 to 1.58
SecondaryProgression Free Survival (PFS)

PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first.

Time frame:
From the date of randomization to the first date of documented progression (approximately 26 months)
Reported as:
Median · Months
Progression Free Survival (PFS)
MonthsFixed Ratio CombinationSequential Combination
Progression Free Survival (PFS)10.25 (2.96 to NA)NA (4.96 to NA)
Statistical analysis
  • Fixed Ratio Combination vs Sequential Combination · Hazard ratio (hr): 1.36 · 95% CI 0.78 to 2.37Stratified Cox proportional hazard model
PrimaryPercentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)

This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction broad scope SMQ. Such AEs include any acute systemic reaction characterized by a large list of terms, including (but not limited to) pruritus, urticaria, flushing, hypotension, respiratory distress, and vascular insufficiency. It also includes other signs and symptoms such as asthma, choking sensation, coughing, sneezing, and difficulty breathing due to laryngeal spasm and/or bronchospasm. Less frequent clinical presentations are also captured and include hyperventilation, sensation of foreign body, and ocular edema.

Time frame:
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Reported as:
Number · Percent of Participants
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)
Percent of ParticipantsFixed Ratio CombinationSequential Combination
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)15.1 (6.7 to 27.6)17.0 (8.1 to 29.8)
Statistical analysis
  • Fixed Ratio Combination vs Sequential Combination · Cochran-mantel-haenszel odds ratio: 0.87 · 95% CI 0.30 to 2.49Fixed Ratio Combination over Sequential Combination
  • Fixed Ratio Combination vs Sequential Combination · Percent difference in incidence rates: -1.9 · 95% CI -16.0 to 12.2Fixed Ratio Combination over Sequential Combination

Adverse events

Collected over From first dose to 100 days following administration of the last dose (approximately 27 months).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Fixed Ratio Combination14/53 (26.4%)35/53 (66%)51/53 (96.2%)
Sequential Combination14/53 (26.4%)35/53 (66%)51/53 (96.2%)
Most frequent serious events
Showing 10 of 84
Most frequent serious events
EventFixed Ratio CombinationSequential Combination
PyrexiaGeneral disorders8/530/53
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/537/53
Hepatocellular injuryHepatobiliary disorders6/533/53
ColitisGastrointestinal disorders4/534/53
Immune-mediated enterocolitisGastrointestinal disorders3/531/53
VomitingGastrointestinal disorders3/531/53
ArthralgiaMusculoskeletal and connective tissue disorders3/531/53
DyspnoeaRespiratory, thoracic and mediastinal disorders0/533/53
PneumonitisRespiratory, thoracic and mediastinal disorders3/531/53
ThyroiditisEndocrine disorders2/531/53
Most frequent other events
Showing 10 of 60
Most frequent other events
EventFixed Ratio CombinationSequential Combination
DiarrhoeaGastrointestinal disorders16/5325/53
AstheniaGeneral disorders17/5320/53
PyrexiaGeneral disorders14/5318/53
PruritusSkin and subcutaneous tissue disorders9/5317/53
HeadacheNervous system disorders8/5315/53
RashSkin and subcutaneous tissue disorders15/5312/53
CoughRespiratory, thoracic and mediastinal disorders13/537/53
NauseaGastrointestinal disorders9/5312/53
VomitingGastrointestinal disorders9/5312/53
HypothyroidismEndocrine disorders11/538/53

Baseline characteristics

All treated participants

Age, Continuous
Age, Continuous(years)Fixed Ratio CombinationSequential CombinationTotal
Mean58.1 ± 14.556.3 ± 14.657.2 ± 14.5
Sex: Female, Male
Sex: Female, Male(Participants)Fixed Ratio CombinationSequential CombinationTotal
Female182644
Male352762
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Fixed Ratio CombinationSequential CombinationTotal
Hispanic or Latino112
Not Hispanic or Latino262854
Unknown or Not Reported262450
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Fixed Ratio CombinationSequential CombinationTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American101
White485098
More than one race000
Unknown or Not Reported437
08

Study locations

16 sites
  • Melanoma Institute Australia
    North Sydney, New South Wales, Australia
  • Greenslopes Private Hospital
    Greenslopes, Queensland, Australia
  • Cabrini Hospital
    Malvern, Victoria, Australia
  • Local Institution
    Lyon Cedex 08, 69373, France
  • Hopital De La Timone
    Marseille Cedex 5, 13385, France
  • Local Institution
    Nantes Cedex 1, 44093, France
  • Local Institution
    Paris Cedex 14, 75679, France
  • Hopital Saint Louis
    Paris, 75475, France
  • Hopital Trousseau - Chru Tours
    Tours, 37044, France
  • Istituto Nazionale Per La Ricerca Sul Cancro - Oncologia Med
    Genova, 16128, Italy
  • Istituto Scientifico Romagnolo Per Lo Studio E Cura Tumori
    Meldola (FC), 47014, Italy
  • Istituto Europeo Di Oncologia
    Milan, 20141, Italy
  • Azienda Ospedaliera Citta della Salute e della Scienza
    Torino, 10137, Italy
  • Local Institution
    Barcelona, 08036, Spain
  • Local Institution
    Madrid, 28007, Spain
  • Local Institution
    Sevilla, 41071, Spain
09

References and documents

Study documents

  • Study protocol · Aug 18, 2017
  • Statistical analysis plan · Oct 23, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 17, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02905266
Lead sponsor
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Sep 19, 2016
Start date
Oct 27, 2016
Primary completion
Oct 23, 2017
Completion
Oct 25, 2019
Results posted
Jan 8, 2019
Last update
Dec 17, 2020

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Nov 2020. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Melanoma→

Other studies from this sponsor

Bristol-Myers Squibb

Start the discussion