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NCT03029780: CheckMate 800

An Investigational Immuno-Therapy Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma

Completed Phase 2 Results posted Last updated 29 June 2022
What this trial tests

Phase 2 trial testing Opdivo in Renal Cell Carcinoma in 104 participants. Completed in 15 June 2021.

Timeline
16 February 2017
Primary endpoint
27 November 2017
15 June 2021

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment104
Start date16 February 2017
Primary completion27 November 2017
Estimated completion15 June 2021
Sites11 locations across Chile, United States, Australia

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Renal Cell Carcinoma. 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.

The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period Primary · From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)

The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).

GroupValue95% CI
Arm A: Fixed Ratio Combination11.54.4 – 23.4
Arm B: Sequential Combination11.54.4 – 23.4
The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period Secondary · From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)

The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).

GroupValue95% CI
Arm A: Fixed Ratio Combination00.0 – 6.8
Arm B: Sequential Combination00.0 – 6.8
The Percentage of Participants With Drug Related Grade 3-5 Adverse Events Secondary · From first dose to 30 days after last dose of study therapy (up to approximately 48 months)

The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.

GroupValue95% CI
Arm A: Fixed Ratio Combination48.134.0 – 62.4
Arm B: Sequential Combination42.328.7 – 56.8
The Percentage of Participants With All Causality Grade 3-5 Adverse Events Secondary · From first dose to 30 days after last dose of study therapy (up to approximately 48 months)

The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria

GroupValue95% CI
Arm A: Fixed Ratio Combination73.159.0 – 84.4
Arm B: Sequential Combination65.450.9 – 78.0
Objective Response Rate (ORR) Secondary · From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months)

The percentage 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 first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all targe

GroupValue95% CI
Arm A: Fixed Ratio Combination50.035.8 – 64.2
Arm B: Sequential Combination32.720.3 – 47.1
Progression Free Survival (PFS) Secondary · From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months)

The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the dat

GroupValue95% CI
Arm A: Fixed Ratio Combination12.069.92 – 18.23
Arm B: Sequential Combination7.693.42 – 11.33
Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab Secondary · pre-dose on day 1 of cycle 2 and 4

Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks

Ipilimumab - Cycle 2 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination3.92± 28.9
Arm B: Sequential Combination3.43± 43.1
Ipilimumab - Cycle 4 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination5.90± 37.8
Arm B: Sequential Combination5.39± 39.8
Nivolumab - Cycle 2 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination16.2± 29.1
Arm B: Sequential Combination16.1± 46.3
Nivolumab - Cycle 4 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination28.5± 35.3
Arm B: Sequential Combination30.5± 43.1
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab Secondary · EOI on day 1 of cycle 1, 2, and 4

Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks

Ipilimumab - Cycle 1 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination17.6± 23.7
Arm B: Sequential Combination13.4± 61.1
Ipilimumab - Cycle 2 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination21.4± 24.8
Arm B: Sequential Combination15.6± 37.9
Ipilimumab - Cycle 4 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination24.9± 31.3
Arm B: Sequential Combination19.5± 38.5
Nivolumab - Cycle 1 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination57.1± 22.4
Arm B: Sequential Combination60.7± 23.0
Nivolumab - Cycle 2 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination70.6± 27.6
Arm B: Sequential Combination79.5± 71.9
Nivolumab - Cycle 4 Day 1
GroupValue95% CI
Arm A: Fixed Ratio Combination85.1± 30.1
Arm B: Sequential Combination88.9± 55.1

Adverse events — posted to ClinicalTrials.gov

Time frame: From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Fixed Ratio Combination
Serious: 27/52 (52%)
Deaths: 26/52
Arm B: Sequential Combination
Serious: 25/52 (48%)
Deaths: 29/52

Serious adverse events (62 terms)

ReactionSystemArm A: Fixed Ratio Combina…Arm B: Sequential Combinat…
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HypophysitisEndocrine disorders
PyrexiaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
MyocarditisCardiac disorders
Adrenocortical insufficiency acuteEndocrine disorders
DiarrhoeaGastrointestinal disorders
Urinary tract infectionInfections and infestations
Acute coronary syndromeCardiac disorders
Acute myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Cardiac arrestCardiac disorders
CardiomegalyCardiac disorders
Coronary artery diseaseCardiac disorders
Myocardial infarctionCardiac disorders
Myocardial ischaemiaCardiac disorders
TachycardiaCardiac disorders
HyperthyroidismEndocrine disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
ColitisGastrointestinal disorders
EnteritisGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
HaematemesisGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Other adverse events (55 terms — click to expand)

ReactionSystemArm A: Fixed Ratio Combina…Arm B: Sequential Combinat…
FatigueGeneral disorders
RashSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Lipase increasedInvestigations
DiarrhoeaGastrointestinal disorders
HypothyroidismEndocrine disorders
HyperglycaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
Amylase increasedInvestigations
Blood creatinine increasedInvestigations
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
HeadacheNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
HyperthyroidismEndocrine disorders
ConstipationGastrointestinal disorders
AstheniaGeneral disorders
Oedema peripheralGeneral disorders
HepatotoxicityHepatobiliary disorders
BronchitisInfections and infestations
Weight decreasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
EosinophiliaBlood and lymphatic system disorders
HypophysitisEndocrine disorders
PyrexiaGeneral disorders
NasopharyngitisInfections and infestations
Infusion related reactionInjury, poisoning and procedural complications
Blood cholesterol increasedInvestigations
Blood sodium decreasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
Adrenal insufficiencyEndocrine disorders
HypersensitivityImmune system disorders

Most-reported serious reactions: Malignant neoplasm progression, Hypophysitis, Pyrexia, Hyperglycaemia, Myocarditis, Adrenocortical insufficiency acute, Diarrhoea, Urinary tract infection.

Data from ClinicalTrials.gov NCT03029780 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate safety and efficacy of different administration regimens of nivolumab plus ipilimumab in subjects with renal cell carcinoma.

Publications & conference data

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

  1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  2. Mechanisms, combination therapy, and biomarkers in cancer immunotherapy resistance.
    Yang M, Cui M, Sun Y, Liu S, et al · · 2024 · cited 50× · PMID 38898505 · DOI 10.1186/s12964-024-01711-w
  3. Ipilimumab in combination with nivolumab for the treatment of renal cell carcinoma.
    Gao X, McDermott DF. · · 2018 · cited 47× · PMID 30124333 · DOI 10.1080/14712598.2018.1513485
  4. 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
  5. Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy.
    Jahangir M, Yazdani O, Yazdani O, Kahrizi MS, et al · · 2022 · cited 15× · PMID 36510217 · DOI 10.1186/s12935-022-02816-3
  6. PD-1/PD-L1 inhibitors-based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies.
    Ding L, Dong HY, Zhou TR, Wang YH, et al · · 2021 · cited 15× · PMID 34382349 · DOI 10.1002/cam4.4190
  7. Safety and efficacy of first-line nivolumab plus ipilimumab alternating with nivolumab monotherapy in patients with advanced renal cell carcinoma: the non-randomised, open-label, phase IIIb/IV CheckMate 920 trial.
    George DJ, Spigel DR, Gordan LN, Kochuparambil ST, et al · · 2022 · cited 4× · PMID 36104138 · DOI 10.1136/bmjopen-2021-058396
  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 Opdivo

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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