Renal Cell Carcinoma
Conditions
Brief summary
This study will generate safety data on Nivolumab given by itself in treatment of advanced Renal Cell Carcinoma (RCC). The primary objective of this study is to assess immune related side effects, also known as immune-mediated adverse events (IMAEs), in patients treated with Nivolumab.
Interventions
DRUGNivolumab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced or Metastatic renal cell carcinoma (RCC) * Predominant clear cell histology: 1. At least 1 but no more than 2 prior systemic anti vascular endothelial growth factor (anti-VEGF) treatments 2. No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting 3. Subjects with prior treatment with a mechanistic target of rapamycin (mTOR) are eligible * Non-clear cell histology: 0-3 prior systemic therapies and may include mTOR inhibitor * Brain metastases allowed if asymptomatic, without edema, and not receiving corticosteroids or radiation * Performance Status (PS): ≥ 70% Karnofsky Performance Scale (KPS) * All Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic scores allowed
Exclusion criteria
* Subjects with any active autoimmune disease or a history of known autoimmune disease * History of severe hypersensitivity reaction to other monoclonal antibodies * Prior malignancy, active within the last 3 years, except for locally curable cancers which have been apparently cured * Known HIV or AIDS-related illness * Any positive tests for Hepatitis B or Hepatitis C virus indicating acute or chronic infection Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Up to 100 days of the last dose of study drug (Approximately 2 years) | IMAEs were tabulated using worst grade per Common Terminology Criteria for Adverse Events, National Cancer Institute (NCI CTCAE) Version 4.0 criteria by system organ class and MedDRA version 20.1 preferred term. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events | From onset of grade 3-5 IMAEs to resolution of IMAEs (Approximately 4 years and 7 months) | Time-to resolution of grade 3-5 AE was defined as the longest time from onset to complete resolution or improvement to the grade at baseline among all clustered select AEs in the category experienced by the participant. Events which worsened into grade 5 events (death) or have a resolution date equal to the date of death are considered unresolved. If a clustered AE is considered as unresolved, the resolution date will be censored to the last known date alive. |
| Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months) | Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil |
| Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events | Up to 100 days of the last dose of study drug (Approximately 10 months up to 26 months) | Time to onset was calculated from first dosing date to the event onset date. If a participant never experienced the given AE, the participant will be censored at the last contact date. |
| Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | From the initiation of Immune modulating medication to discontinuation (approximately 4 years and 9 months).) | Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil. |
| Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Up to 100 days of the last dose of study drug (Approximately 2 years) | Percentage of participants with a resolution of IMAEs after initiating immune modulating medication. |
| Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months) | Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil |
Countries
United States
Participant flow
Pre-assignment details
142 Participants were treated
Participants by arm
| Arm | Count |
|---|---|
| Clear Cell Histology Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. | 97 |
| Non-Clear Cell Histology Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. | 44 |
| Brain Metastasis Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. | 1 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | AE unrelated to study drug | 5 | 2 | 0 |
| Overall Study | Disease Progression | 64 | 32 | 1 |
| Overall Study | other reasons | 11 | 4 | 0 |
| Overall Study | participant no longer meets study criteria | 1 | 0 | 0 |
| Overall Study | participant request to discontinue study treatment | 2 | 0 | 0 |
| Overall Study | participant withdrew consent | 2 | 2 | 0 |
| Overall Study | Poor/Non Comlpiance | 0 | 1 | 0 |
| Overall Study | study drug toxicity | 12 | 3 | 0 |
Baseline characteristics
| Characteristic | Clear Cell Histology | Non-Clear Cell Histology | Brain Metastasis | Total |
|---|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 10.33 | 61.4 Years STANDARD_DEVIATION 12.88 | 32 Years | 63.5 Years STANDARD_DEVIATION 11.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 4 Participants | 1 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 86 Participants | 39 Participants | 0 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 90 Participants | 34 Participants | 1 Participants | 125 Participants |
| Sex: Female, Male Female | 31 Participants | 12 Participants | 1 Participants | 44 Participants |
| Sex: Female, Male Male | 66 Participants | 32 Participants | 0 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 63 / 97 | 29 / 44 | 1 / 1 | 93 / 142 |
| other Total, other adverse events | 91 / 97 | 41 / 44 | 1 / 1 | 133 / 142 |
| serious Total, serious adverse events | 54 / 97 | 19 / 44 | 0 / 1 | 73 / 142 |
Outcome results
Primary
Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs)
IMAEs were tabulated using worst grade per Common Terminology Criteria for Adverse Events, National Cancer Institute (NCI CTCAE) Version 4.0 criteria by system organ class and MedDRA version 20.1 preferred term.
Time frame: Up to 100 days of the last dose of study drug (Approximately 2 years)
Population: Analysis was performed in all treated participants who received any dose of nivolumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypophysitis (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypophysitis (Grade 3-4) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Pneumonitis (Grade 3-4) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Nephritis And Renal Dysfunction (Grade 3-4) | 1 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hyperthyroidism (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Pneumonitis (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Rash (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypersensitivity (Grade 3-4) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Adrenal Insufficiency (Grade 3-4) | 1 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypersensitivity (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diabetes mellitus (Grade 3-4) | 3.1 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis (Grade 3-4) | 1 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Nephritis And Renal Dysfunction (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Adrenal Insufficiency (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diabetes mellitus (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hyperthyroidism (Grade 3-4) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypothyroidism (Grade 3-4) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hepatitis (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypothyroidism (Grade 5) | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Rash (Grade 3-4) | 1 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hepatitis (Grade 3-4) | 4.1 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Adrenal Insufficiency (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Nephritis And Renal Dysfunction (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Rash (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Rash (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diabetes mellitus (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diabetes mellitus (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypothyroidism (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypothyroidism (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypophysitis (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Pneumonitis (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Pneumonitis (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypersensitivity (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypersensitivity (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hyperthyroidism (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hepatitis (Grade 5) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Adrenal Insufficiency (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hepatitis (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Nephritis And Renal Dysfunction (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypophysitis (Grade 3-4) | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hyperthyroidism (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypothyroidism (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypophysitis (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypersensitivity (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Adrenal Insufficiency (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diabetes mellitus (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypersensitivity (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Adrenal Insufficiency (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Rash (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hepatitis (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Nephritis And Renal Dysfunction (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Rash (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diabetes mellitus (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Nephritis And Renal Dysfunction (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hepatitis (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Pneumonitis (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hyperthyroidism (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Diarrhea/Colitis (Grade 5) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypophysitis (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hyperthyroidism (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Pneumonitis (Grade 3-4) | 0 Percentage of participants |
| Brain Metastasis | Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) | Hypothyroidism (Grade 5) | 0 Percentage of participants |
Secondary
Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events
Time to onset was calculated from first dosing date to the event onset date. If a participant never experienced the given AE, the participant will be censored at the last contact date.
Time frame: Up to 100 days of the last dose of study drug (Approximately 10 months up to 26 months)
Population: Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Clear Cell Histology | Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events | Adrenal Insufficiency | 76.0 Days |
| Clear Cell Histology | Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events | Diabetes Mellitus | 89.0 Days |
| Clear Cell Histology | Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events | Hepatitis | 84.5 Days |
| Clear Cell Histology | Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events | Nephritis And Renal Dysfunction | 43.0 Days |
| Clear Cell Histology | Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events | Rash | 7.0 Days |
| Clear Cell Histology | Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events | Diarrhea/Colitis | 645.0 Days |
Secondary
Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events
Time-to resolution of grade 3-5 AE was defined as the longest time from onset to complete resolution or improvement to the grade at baseline among all clustered select AEs in the category experienced by the participant. Events which worsened into grade 5 events (death) or have a resolution date equal to the date of death are considered unresolved. If a clustered AE is considered as unresolved, the resolution date will be censored to the last known date alive.
Time frame: From onset of grade 3-5 IMAEs to resolution of IMAEs (Approximately 4 years and 7 months)
Population: Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Clear Cell Histology | Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events | Rash | 23.0 Days |
| Clear Cell Histology | Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events | Diarrhea/Colitis | 154.0 Days |
| Clear Cell Histology | Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events | Adrenal Insufficiency | NA Days |
| Clear Cell Histology | Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events | Hepatitis | 31.5 Days |
| Clear Cell Histology | Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events | Nephritis And Renal Dysfunction | 22.0 Days |
Secondary
Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade)
Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil
Time frame: Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months)
Population: Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Hypersensitivity | 66.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Hyperthyroidism | 12.5 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Hepatitis | 41.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Adrenal Insufficiency | 100 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Nephritis And Renal Dysfunction | 13.6 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Rash | 38.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Pneumonitis | 66.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Diarrhea/Colitis | 5.3 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Hypophysitis | 100.0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Diarrhea/Colitis | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Hepatitis | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Nephritis And Renal Dysfunction | 33.3 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Rash | 25.0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Pneumonitis | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) | Participants with Hyperthyroidism | 0 Percentage of participants |
Secondary
Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event
Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil
Time frame: Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months)
Population: Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Adrenal Insufficiency | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Nephritis And Renal Dysfunction | 9.1 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Rash | 6.5 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Pneumonitis | 66.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Diarrhea/Colitis | 5.3 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Hepatitis | 41.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Hypersensitivity | 66.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Hyperthyroidism | 12.5 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Diarrhea/Colitis | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Nephritis And Renal Dysfunction | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Hypophysitis | 100.0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Rash | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Hepatitis | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Pneumonitis | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event | Participants with Hyperthyroidism | 0 Percentage of participants |
Secondary
Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication
Percentage of participants with a resolution of IMAEs after initiating immune modulating medication.
Time frame: Up to 100 days of the last dose of study drug (Approximately 2 years)
Population: Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Hypersensitivity | 100 Percentage of participants |
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Hyperthyroidism | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Pneumonitis | 100 Percentage of participants |
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Adrenal Insufficiency | 0 Percentage of participants |
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Nephritis And Renal Dysfunction | 66.7 Percentage of participants |
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Diarrhea/Colitis | 100 Percentage of participants |
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Rash | 83.3 Percentage of participants |
| Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Hepatitis | 100 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Hypophysitis | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Nephritis And Renal Dysfunction | 0 Percentage of participants |
| Non-Clear Cell Histology | Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication | Rash | 50 Percentage of participants |
Secondary
Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event
Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil.
Time frame: From the initiation of Immune modulating medication to discontinuation (approximately 4 years and 9 months).)
Population: Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Nephritis And Renal Dysfunction | 1.14 Weeks |
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Adrenal Insufficiency | 241.14 Weeks |
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Hypersensitivity | 0.1 Weeks |
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Hyperthyroidism | 8.4 Weeks |
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Rash | 9.29 Weeks |
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Pneumonitis | 111.07 Weeks |
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Diarrhea/Colitis | 7.9 Weeks |
| Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Hepatitis | 7.00 Weeks |
| Non-Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Nephritis And Renal Dysfunction | 1.9 Weeks |
| Non-Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Hypophysitis | 81.9 Weeks |
| Non-Clear Cell Histology | Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event | Rash | 137.43 Weeks |