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An Investigational Immuno-Therapy Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma (CheckMate 800)

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ClinicalTrials.gov Identifier: NCT03029780
Recruitment Status : Unknown
Verified November 2018 by Bristol-Myers Squibb.
Recruitment status was:  Active, not recruiting
First Posted : January 24, 2017
Results First Posted : December 19, 2018
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Cell Carcinoma
Interventions Biological: Opdivo
Biological: Yervoy
Enrollment 118
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A: Fixed Ratio Combination Arm B: Sequential Combination
Hide Arm/Group Description BMS-986237 Co-administration fixed ratio combination (FRC) Nivolumab 3mg/kg + Ipilimumab 1 mg/kg IV (Sequential)
Period Title: Overall Study
Started 52 52
Completed [1] 46 41
Not Completed 6 11
Reason Not Completed
Disease Progression             1             3
Study Drug Toxicity             5             5
Adverse Event Unrelated to Study Drug             0             3
[1]
Completed = continuing in the study
Arm/Group Title Arm A: Fixed Ratio Combination Arm B: Sequential Combination Total
Hide Arm/Group Description BMS-986237 Co-administration fixed ratio combination (FRC) Nivolumab 3mg/kg + Ipilimumab 1 mg/kg IV (Sequential) Total of all reporting groups
Overall Number of Baseline Participants 52 52 104
Hide Baseline Analysis Population Description
All treated participants.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 52 participants 104 participants
62.2  (10.9) 62.6  (9.9) 62.4  (10.4)
[1]
Measure Analysis Population Description: All treated participants
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 52 participants 104 participants
Female
10
  19.2%
14
  26.9%
24
  23.1%
Male
42
  80.8%
38
  73.1%
80
  76.9%
[1]
Measure Analysis Population Description: All treated participants
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Count of participants
Number Analyzed 52 participants 52 participants 104 participants
White 46 51 97
Black or African American 1 0 1
Asian 3 0 3
American Indian or Alaska Native 0 0 0
Native Hawaiian or Other Pacific Islander 1 0 1
Other 1 1 2
[1]
Measure Analysis Population Description: All treated participants
1.Primary Outcome
Title Incidence Rate of Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction SMQ Within 2 Days After Any Dose in Combination Period.
Hide Description This incidence rate is defined as the number of participants who experienced at least 1 AE 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) divided by number of treated participants.
Time Frame From the time of randomization to end of combination period (assessed up to November 24th, 2017, approximately 9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Fixed Ratio Combination Arm B: Sequential Combination
Hide Arm/Group Description:
BMS-986237 Co-administration fixed ratio combination (FRC)
Nivolumab 3mg/kg + Ipilimumab 1 mg/kg IV (Sequential)
Overall Number of Participants Analyzed 52 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
11.5
(4.4 to 23.4)
11.5
(4.4 to 23.4)
2.Secondary Outcome
Title Incidence Rate of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ Occurring Within 2 Days After Any Dose in the Part 1 Period
Hide Description This incidence rate is defined similarly to the primary endpoint except that the event rate will be based on terms within the narrow scope SMQ rather than the broad scope.
Time Frame From the time of randomization to end of combination period (assessed up to November 24th, 2017, approximately 9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Fixed Ratio Combination Arm B: Sequential Combination
Hide Arm/Group Description:
BMS-986237 Co-administration fixed ratio combination (FRC)
Nivolumab 3mg/kg + Ipilimumab 1 mg/kg IV (Sequential)
Overall Number of Participants Analyzed 52 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
0
(0.0 to 6.8)
0
(0.0 to 6.8)
3.Secondary Outcome
Title Incidence Rate of Drug Related Grade 3-5 AEs.
Hide Description The drug-related Grade 3 - 5 AE rate is defined as number of participants who experienced at least 1 AE 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, divided by number of treated participants. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.
Time Frame From the time of randomization to end of combination period (assessed up to November 24th, 2017, approximately 9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Fixed Ratio Combination Arm B: Sequential Combination
Hide Arm/Group Description:
BMS-986237 Co-administration fixed ratio combination (FRC)
Nivolumab 3mg/kg + Ipilimumab 1 mg/kg IV (Sequential)
Overall Number of Participants Analyzed 52 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
36.5
(23.6 to 51.0)
38.5
(25.3 to 53.0)
4.Secondary Outcome
Title Incidence Rate of All Causality Grade 3-5 AE
Hide Description The all causality Grade 3 - 5 AE rate is defined as number of participants who experienced at least 1 AE 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, divided by number of treated participants. Evaluated using the NCI CTCAE version 4.0 criteria
Time Frame From the time of randomization to end of combination period (assessed up to November 24th, 2017, approximately 9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Fixed Ratio Combination Arm B: Sequential Combination
Hide Arm/Group Description:
BMS-986237 Co-administration fixed ratio combination (FRC)
Nivolumab 3mg/kg + Ipilimumab 1 mg/kg IV (Sequential)
Overall Number of Participants Analyzed 52 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Particpants
46.2
(32.2 to 60.5)
53.8
(39.5 to 67.8)
5.Secondary Outcome
Title Nivolumab and Ipilimumab Geometric Mean Concentrations at End of Infusion (EOI) and Predose at Cycle 1, 2 and 4
Hide Description To determine pharmacokinetics (PK) comparisons of Nivolumab and Ipilimumab administered as FRC to that of sequentially administered Nivolumab and Ipilimumab. PK will be measured using serum concentration-time data.
Time Frame From the date of first dose to end of combination stage approximately 9 months
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description The ORR is defined as the number of participants with a BOR of CR or PR divided by the number of treated participants. 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 including radiotherapy, tumor-directed surgery, or systemic anticancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment
Time Frame From the date of first dose to end of combination stage approximately 9 months
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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 first dose to end of combination stage approximately 9 months
Outcome Measure Data Not Reported
Time Frame From the date of first dose to end of combination stage (assessed up to November 27th, 2017, approximately 9 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NIVO 3 + IPI 1 FRC NIVO 3 + IPI 1 SEQ
Hide Arm/Group Description BMS-986237 Co-administration fixed ratio combination (FRC) Nivolumab 3mg/kg + Ipilimumab 1 mg/kg IV (Sequential)
All-Cause Mortality
NIVO 3 + IPI 1 FRC NIVO 3 + IPI 1 SEQ
Affected / at Risk (%) Affected / at Risk (%)
Total   1/52 (1.92%)   7/52 (13.46%) 
Hide Serious Adverse Events
NIVO 3 + IPI 1 FRC NIVO 3 + IPI 1 SEQ
Affected / at Risk (%) Affected / at Risk (%)
Total   16/52 (30.77%)   13/52 (25.00%) 
Cardiac disorders     
Atrial fibrillation  1  1/52 (1.92%)  0/52 (0.00%) 
Cardiac arrest  1  1/52 (1.92%)  0/52 (0.00%) 
Myocardial ischaemia  1  1/52 (1.92%)  0/52 (0.00%) 
Myocarditis  1  2/52 (3.85%)  0/52 (0.00%) 
Endocrine disorders     
Adrenocortical insufficiency acute  1  1/52 (1.92%)  1/52 (1.92%) 
Hyperthyroidism  1  1/52 (1.92%)  1/52 (1.92%) 
Hypophysitis  1  0/52 (0.00%)  3/52 (5.77%) 
Gastrointestinal disorders     
Colitis  1  1/52 (1.92%)  0/52 (0.00%) 
Diarrhoea  1  2/52 (3.85%)  0/52 (0.00%) 
Intestinal obstruction  1  1/52 (1.92%)  0/52 (0.00%) 
General disorders     
Chest pain  1  0/52 (0.00%)  1/52 (1.92%) 
Pyrexia  1  2/52 (3.85%)  0/52 (0.00%) 
Hepatobiliary disorders     
Autoimmune hepatitis  1  0/52 (0.00%)  1/52 (1.92%) 
Drug-induced liver injury  1  1/52 (1.92%)  0/52 (0.00%) 
Infections and infestations     
Gastroenteritis  1  2/52 (3.85%)  0/52 (0.00%) 
Herpes zoster  1  0/52 (0.00%)  1/52 (1.92%) 
Lower respiratory tract infection  1  1/52 (1.92%)  0/52 (0.00%) 
Respiratory tract infection viral  1  1/52 (1.92%)  0/52 (0.00%) 
Urinary tract infection  1  0/52 (0.00%)  1/52 (1.92%) 
Injury, poisoning and procedural complications     
Fracture  1  0/52 (0.00%)  1/52 (1.92%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/52 (1.92%)  0/52 (0.00%) 
Hypomagnesaemia  1  1/52 (1.92%)  0/52 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/52 (0.00%)  1/52 (1.92%) 
Pathological fracture  1  0/52 (0.00%)  1/52 (1.92%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  0/52 (0.00%)  3/52 (5.77%) 
Renal and urinary disorders     
Urinary retention  1  0/52 (0.00%)  1/52 (1.92%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/52 (0.00%)  1/52 (1.92%) 
Haemoptysis  1  1/52 (1.92%)  0/52 (0.00%) 
Pleural effusion  1  0/52 (0.00%)  1/52 (1.92%) 
Vascular disorders     
Orthostatic hypotension  1  1/52 (1.92%)  0/52 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NIVO 3 + IPI 1 FRC NIVO 3 + IPI 1 SEQ
Affected / at Risk (%) Affected / at Risk (%)
Total   45/52 (86.54%)   42/52 (80.77%) 
Endocrine disorders     
Hyperthyroidism  1  2/52 (3.85%)  4/52 (7.69%) 
Hypophysitis  1  1/52 (1.92%)  4/52 (7.69%) 
Hypothyroidism  1  9/52 (17.31%)  6/52 (11.54%) 
Gastrointestinal disorders     
Abdominal pain  1  6/52 (11.54%)  2/52 (3.85%) 
Constipation  1  1/52 (1.92%)  4/52 (7.69%) 
Diarrhoea  1  11/52 (21.15%)  5/52 (9.62%) 
Nausea  1  4/52 (7.69%)  4/52 (7.69%) 
Vomiting  1  6/52 (11.54%)  1/52 (1.92%) 
General disorders     
Asthenia  1  4/52 (7.69%)  4/52 (7.69%) 
Fatigue  1  17/52 (32.69%)  10/52 (19.23%) 
Pyrexia  1  2/52 (3.85%)  3/52 (5.77%) 
Hepatobiliary disorders     
Hepatotoxicity  1  4/52 (7.69%)  3/52 (5.77%) 
Infections and infestations     
Bronchitis  1  0/52 (0.00%)  3/52 (5.77%) 
Upper respiratory tract infection  1  5/52 (9.62%)  0/52 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  4/52 (7.69%)  4/52 (7.69%) 
Amylase increased  1  4/52 (7.69%)  4/52 (7.69%) 
Aspartate aminotransferase increased  1  4/52 (7.69%)  4/52 (7.69%) 
Blood creatinine increased  1  2/52 (3.85%)  5/52 (9.62%) 
Blood thyroid stimulating hormone decreased  1  3/52 (5.77%)  1/52 (1.92%) 
Lipase increased  1  6/52 (11.54%)  4/52 (7.69%) 
Metabolism and nutrition disorders     
Decreased appetite  1  4/52 (7.69%)  2/52 (3.85%) 
Hyperglycaemia  1  5/52 (9.62%)  2/52 (3.85%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/52 (3.85%)  4/52 (7.69%) 
Back pain  1  3/52 (5.77%)  2/52 (3.85%) 
Nervous system disorders     
Headache  1  6/52 (11.54%)  6/52 (11.54%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  9/52 (17.31%)  2/52 (3.85%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  11/52 (21.15%)  11/52 (21.15%) 
Rash  1  18/52 (34.62%)  7/52 (13.46%) 
Rash maculo-papular  1  1/52 (1.92%)  3/52 (5.77%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Nivolumab plus Ipilimumab in Subjects with Renal Cell Carcinoma
Organization: Bristol Myer-Squibb
Phone: Please email
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03029780    
Other Study ID Numbers: CA209-800
First Submitted: January 20, 2017
First Posted: January 24, 2017
Results First Submitted: November 27, 2018
Results First Posted: December 19, 2018
Last Update Posted: December 19, 2018