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NCT02905266

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

Completed Phase 3 Results posted Last updated 17 December 2020
What this trial tests

Phase 3 trial testing Nivolumab in Melanoma in 106 participants. Completed in 25 October 2019.

Timeline
27 October 2016
Primary endpoint
23 October 2017
25 October 2019

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment106
Start date27 October 2016
Primary completion23 October 2017
Estimated completion25 October 2019
Sites16 locations across France, Spain, Australia, Italy

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Melanoma. 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.

Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ Secondary · Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

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.

GroupValue95% CI
Fixed Ratio Combination0.00.0 – 6.7
Sequential Combination0.00.0 – 6.7
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs Secondary · Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

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

GroupValue95% CI
Fixed Ratio Combination7.5
Sequential Combination9.4
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs Secondary · From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)

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

GroupValue95% CI
Fixed Ratio Combination69.8
Sequential Combination56.6
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs Secondary · From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)

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

GroupValue95% CI
Fixed Ratio Combination58.5
Sequential Combination47.2
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI) Secondary · 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.
Cycle 1 Day 1
GroupValue95% CI
Fixed Ratio Combination60.4± 93.0
Sequential Combination61.5± 72.3
Cycle 2 Day 1
GroupValue95% CI
Fixed Ratio Combination66.8± 134
Sequential Combination72.1± 71.8
Cycle 4 Day 1
GroupValue95% CI
Fixed Ratio Combination77.9± 94.2
Sequential Combination84.6± 104
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI) Secondary · 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
Cycle 1 Day 1
GroupValue95% CI
Fixed Ratio Combination20.9± 77.3
Sequential Combination21.8± 117
Cycle 2 Day 1
GroupValue95% CI
Fixed Ratio Combination24.2± 122
Sequential Combination22.4± 101
Cycle 4 Day 1
GroupValue95% CI
Fixed Ratio Combination27.9± 79.8
Sequential Combination27.4± 79.9
Geometric Mean Trough Concentration of Ipilimumab Secondary · From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Cycle 2 Day 1
GroupValue95% CI
Fixed Ratio Combination10.8± 30.2
Sequential Combination9.94± 38.9
Cycle 4 Day 1
GroupValue95% CI
Fixed Ratio Combination16.5± 36.9
Sequential Combination13.7± 46.0
Geometric Mean Trough Concentration of Nivolumab Secondary · From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Cycle 2 Day 1
GroupValue95% CI
Fixed Ratio Combination3.94± 56.6
Sequential Combination2.75± 65.9
Cycle 4 Day 1
GroupValue95% CI
Fixed Ratio Combination6.50± 44.6
Sequential Combination4.05± 75.3
Objective Response Rate (ORR) Secondary · Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)

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.

GroupValue95% CI
Fixed Ratio Combination52.838.6 – 66.7
Sequential Combination60.446.0 – 73.5
Progression Free Survival (PFS) Secondary · From the date of randomization to the first date of documented progression (approximately 26 months)

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.

GroupValue95% CI
Fixed Ratio Combination10.252.96 – NA
Sequential CombinationNA4.96 – NA
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Primary · Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

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, sensa

GroupValue95% CI
Fixed Ratio Combination15.16.7 – 27.6
Sequential Combination17.08.1 – 29.8

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose to 100 days following administration of the last dose (approximately 27 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fixed Ratio Combination
Serious: 35/53 (66%)
Deaths: 14/53
Sequential Combination
Serious: 35/53 (66%)
Deaths: 14/53

Serious adverse events (84 terms)

ReactionSystemFixed Ratio CombinationSequential Combination
PyrexiaGeneral disorders
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular injuryHepatobiliary disorders
ColitisGastrointestinal disorders
Immune-mediated enterocolitisGastrointestinal disorders
VomitingGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
ThyroiditisEndocrine disorders
Autoimmune colitisGastrointestinal disorders
Intestinal perforationGastrointestinal disorders
Autoimmune hepatitisHepatobiliary disorders
HepatitisHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
ErysipelasInfections and infestations
Meningitis asepticInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Transaminases increasedInvestigations
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Angina pectorisCardiac disorders
Atrial fibrillationCardiac disorders
Adrenal insufficiencyEndocrine disorders
HypophysitisEndocrine disorders
Other adverse events (60 terms — click to expand)

ReactionSystemFixed Ratio CombinationSequential Combination
DiarrhoeaGastrointestinal disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
PruritusSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
RashSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
HypothyroidismEndocrine disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
Rash pruriticSkin and subcutaneous tissue disorders
VitiligoSkin and subcutaneous tissue disorders
HyperthyroidismEndocrine disorders
Influenza like illnessGeneral disorders
Alanine aminotransferase increasedInvestigations
Lipase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Hepatocellular injuryHepatobiliary disorders
AnaemiaBlood and lymphatic system disorders
Dry mouthGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Abdominal painGastrointestinal disorders
ColitisGastrointestinal disorders
Oedema peripheralGeneral disorders
Amylase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
ParaesthesiaNervous system disorders
InsomniaPsychiatric disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ErythemaSkin and subcutaneous tissue disorders
Night sweatsSkin and subcutaneous tissue disorders
HypophysitisEndocrine disorders
Abdominal distensionGastrointestinal disorders
ChillsGeneral disorders
HepatitisHepatobiliary disorders

Most-reported serious reactions: Pyrexia, Malignant neoplasm progression, Hepatocellular injury, Colitis, Immune-mediated enterocolitis, Vomiting, Arthralgia, Dyspnoea.

Data from ClinicalTrials.gov NCT02905266 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
    Naimi A, Mohammed RN, Raji A, Chupradit S, et al · · 2022 · cited 350× · PMID 35392976 · DOI 10.1186/s12964-022-00854-y
  2. Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC).
    Chae YK, Arya A, Iams W, Cruz MR, et al · · 2018 · cited 336× · PMID 29769148 · DOI 10.1186/s40425-018-0349-3
  3. Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma.
    Khair DO, Bax HJ, Mele S, Crescioli S, et al · · 2019 · cited 181× · PMID 30941125 · DOI 10.3389/fimmu.2019.00453
  4. Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies.
    Park JA, Cheung NV. · · 2017 · cited 81× · PMID 28622628 · DOI 10.1016/j.ctrv.2017.05.006
  5. Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity.
    Archilla-Ortega A, Domuro C, Martin-Liberal J, Muñoz P. · · 2022 · cited 61× · PMID 35164813 · DOI 10.1186/s13046-022-02264-x
  6. Understanding of Immune Escape Mechanisms and Advances in Cancer Immunotherapy.
    Aktar N, Yueting C, Abbas M, Zafar H, et al · · 2022 · cited 32× · PMID 35401745 · DOI 10.1155/2022/8901326
  7. Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical trials.
    Johnson CB, Win SY. · · 2018 · cited 26× · PMID 29632719 · DOI 10.1080/2162402x.2017.1408744
  8. Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800).
    Menzies AM, Salman P, Frontera OA, Pook D, et al · · 2025 · cited 1× · PMID 40614118 · DOI 10.1002/cncr.35962

Verify or expand the search:

Other trials of Nivolumab

Trials testing the same drug.

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Currently open trials in the same condition.

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Trials by the same sponsor.

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