A Phase 2 interventional study of Opdivo and Yervoy in Renal Cell Carcinoma, sponsored by Bristol-Myers Squibb. Completed at 11 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-29.
Sponsored by Bristol-Myers Squibb · Phase 2, Interventional, and Treatment
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.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 104 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.
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Inclusion Criteria:
Exclusion Criteria:
Other protocol defined inclusion/exclusion criteria could apply
Nivolumab and Ipilimumab Co-Administration
Biological: Opdivo · Biological: Yervoy
Nivolumab and Ipilimumab Sequential Administration
Biological: Opdivo · Biological: Yervoy
Specified dose on specified days
Also known as: Nivolumab
Specified dose on specified days
Also known as: Ipilimumab
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
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).
Time frame: From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)
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
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).
Time frame: 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 With Drug Related Grade 3-5 Adverse Events
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.
Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 48 months)
The Percentage of Participants With All Causality Grade 3-5 Adverse Events
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
Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 48 months)
Objective Response Rate (ORR)
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 target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months)
Progression Free Survival (PFS)
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 date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)
Time frame: From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months)
Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab
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
Time frame: pre-dose on day 1 of cycle 2 and 4
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab
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
Time frame: EOI on day 1 of cycle 1, 2, and 4
| Milestone | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| Started | 52 | 52 |
| Completed | 1 | 1 |
| Not completed | 51 | 51 |
| Withdrew: Disease progression | 20 | 22 |
| Withdrew: Study drug toxicity | 15 | 11 |
| Withdrew: Adverse event unrelated to study drug | 2 | 3 |
| Withdrew: Participant request to discontinue study treatment | 4 | 1 |
| Withdrew: Maximum clinical benefit | 1 | 0 |
| Withdrew: Participant no longer meets study criteria | 0 | 1 |
| Withdrew: Other reasons | 6 | 6 |
| Withdrew: Not reported | 1 | 1 |
| Withdrew: Death | 2 | 6 |
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).
| Percentage of Participants | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| 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 | 11.5 (4.4 to 23.4) | 11.5 (4.4 to 23.4) |
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).
| Percentage of Participants | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| 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 | 0 (0.0 to 6.8) | 0 (0.0 to 6.8) |
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.
| Percentage of Participants | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| The Percentage of Participants With Drug Related Grade 3-5 Adverse Events | 48.1 (34.0 to 62.4) | 42.3 (28.7 to 56.8) |
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
| Percentage of Particpants | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| The Percentage of Participants With All Causality Grade 3-5 Adverse Events | 73.1 (59.0 to 84.4) | 65.4 (50.9 to 78.0) |
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 target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| Percentage of Particpants | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| Objective Response Rate (ORR) | 50.0 (35.8 to 64.2) | 32.7 (20.3 to 47.1) |
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 date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)
| Months | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| Progression Free Survival (PFS) | 12.06 (9.92 to 18.23) | 7.69 (3.42 to 11.33) |
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
| ug/mL | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| Ipilimumab - Cycle 2 Day 1 | 3.92 ± 28.9 | 3.43 ± 43.1 |
| Ipilimumab - Cycle 4 Day 1 | 5.90 ± 37.8 | 5.39 ± 39.8 |
| Nivolumab - Cycle 2 Day 1 | 16.2 ± 29.1 | 16.1 ± 46.3 |
| Nivolumab - Cycle 4 Day 1 | 28.5 ± 35.3 | 30.5 ± 43.1 |
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
| ug/mL | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| Ipilimumab - Cycle 1 Day 1 | 17.6 ± 23.7 | 13.4 ± 61.1 |
| Ipilimumab - Cycle 2 Day 1 | 21.4 ± 24.8 | 15.6 ± 37.9 |
| Ipilimumab - Cycle 4 Day 1 | 24.9 ± 31.3 | 19.5 ± 38.5 |
| Nivolumab - Cycle 1 Day 1 | 57.1 ± 22.4 | 60.7 ± 23.0 |
| Nivolumab - Cycle 2 Day 1 | 70.6 ± 27.6 | 79.5 ± 71.9 |
| Nivolumab - Cycle 4 Day 1 | 85.1 ± 30.1 | 88.9 ± 55.1 |
Collected over 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). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A: Fixed Ratio Combination | 26/52 (50%) | 27/52 (51.9%) | 49/52 (94.2%) |
| Arm B: Sequential Combination | 29/52 (55.8%) | 25/52 (48.1%) | 48/52 (92.3%) |
| Event | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 5/52 | 5/52 |
| HypophysitisEndocrine disorders | 0/52 | 3/52 |
| PyrexiaGeneral disorders | 3/52 | 0/52 |
| HyperglycaemiaMetabolism and nutrition disorders | 3/52 | 0/52 |
| MyocarditisCardiac disorders | 2/52 | 0/52 |
| Adrenocortical insufficiency acuteEndocrine disorders | 2/52 | 1/52 |
| DiarrhoeaGastrointestinal disorders | 2/52 | 0/52 |
| Urinary tract infectionInfections and infestations | 0/52 | 2/52 |
| Acute coronary syndromeCardiac disorders | 0/52 | 1/52 |
| Acute myocardial infarctionCardiac disorders | 0/52 | 1/52 |
| Event | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination |
|---|---|---|
| FatigueGeneral disorders | 24/52 | 15/52 |
| RashSkin and subcutaneous tissue disorders | 20/52 | 10/52 |
| PruritusSkin and subcutaneous tissue disorders | 15/52 | 15/52 |
| Lipase increasedInvestigations | 14/52 | 11/52 |
| DiarrhoeaGastrointestinal disorders | 13/52 | 11/52 |
| HypothyroidismEndocrine disorders | 12/52 | 8/52 |
| HyperglycaemiaMetabolism and nutrition disorders | 12/52 | 3/52 |
| CoughRespiratory, thoracic and mediastinal disorders | 12/52 | 5/52 |
| Amylase increasedInvestigations | 11/52 | 9/52 |
| Blood creatinine increasedInvestigations | 10/52 | 11/52 |
All treated participants.
| Age, Continuous(Years) | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination | Total |
|---|---|---|---|
| Mean | 62.2 ± 10.9 | 62.6 ± 9.9 | 62.4 ± 10.4 |
| Sex: Female, Male(Participants) | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination | Total |
|---|---|---|---|
| Female | 10 | 14 | 24 |
| Male | 42 | 38 | 80 |
| Race/Ethnicity, Customized(Count of participants) | Arm A: Fixed Ratio Combination | Arm B: Sequential Combination | Total |
|---|---|---|---|
| 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 |
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