Non Small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
The purpose of this study is to estimate the incidence and characterize the outcome of high grade, select adverse events in subjects with advanced or metastatic NSCLC treated with Nivolumab.
Interventions
DRUGNivolumab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Target Population * Subjects with histologically-or cytologically-documented NSCLC \[squamous (SQ) or nonsquamous (NSQ)\] who present with Stage IIIB/Stage IV disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiotherapy for locally advanced disease) * Subjects must have experienced disease progression or recurrence during or after at least one systemic therapy for advanced or metastatic disease * Each subsequent line of therapy must be preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy * Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy * Subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible * Subjects with recurrent disease \>6 months after platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence are eligible * Subjects with non-squamous histology must be tested for Epithelial Growth Factor Receptor (EGFR) mutations (including, but not limited to, deletions in exon 19 and exon 21 \[L858R\] substitution) and Anaplastic Lymphoma Kinase (ALK) rearrangement if tests have not been previously performed. Subjects with progressive disease during or after EGFR or ALK tyrosine kinase inhibitor (TKI) regimens are eligible. Subjects are eligible if genetic test results are indeterminate or if no tumor tissue is available or accessible for testing as long as they have received one prior systemic therapy * Experimental therapies when given as separate regimen are considered as separate line of therapy * Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria (radiographic tumor assessment performed within 28 days of first dose of study drug) or clinically apparent disease that the investigator can follow for response per RECIST 1.1 * Eastern Cooperative Oncology Arm (ECOG) performance status (PS) * PS 0 to 1 * PS 2
Exclusion criteria
1. Target Disease Exceptions * Subjects with active central nervous system (CNS) metastases are excluded * Subjects with carcinomatous meningitis 2. Medical History and Concurrent Diseases * Subjects with a history of interstitial lung disease * Subjects with active, known or suspected autoimmune disease * Subject whom participated in either arm of the following clinical trials CA209-017, CA209-057, CA209-026, and CA184-104 or received prior treatment with anti-programmed death 1 (PD-1) or anti-programmed death-ligand 1 (PDL1) experimental agents 3. Prohibited Treatments and/or Restricted Therapies * Ongoing or planned administration of anti-cancer therapies other than those specified in this study * Use of corticosteroids or other immunosuppressive medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) | A treatment related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that has a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Resolution of Select Adverse Events (Grade 3-5) | From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) | The time from the onset of any select adverse event of interest to its resolution or stabilization. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death. |
| The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) | The number of participants receiving medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death. |
| Median Time to Onset of Select Adverse Events (Grade 3-5) | From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) | The time from first dose to the first occurrence of any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death. |
| The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | From first dose first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) | The duration of time participants received medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death. |
| The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death. |
| The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) | The number of participants receiving \> 40mg prednisone equivalents for any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death. |
Countries
Canada, United States
Participant flow
Pre-assignment details
After 1 year of treatment, participants who are still on treatment are randomized to Cohort A or Cohort B.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Nivolumab Monotherapy Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Each 14 day dosing period will constitute a cycle. After 1 year (52 weeks) of treatment all participants will continue to receive treatment until disease progression, unacceptable toxicity, or withdrawal of informed consent. | 127 |
| Cohort B: Nivolumab Monotherapy Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Each 14 day dosing period will constitute a cycle. After 1 year (52 weeks) of treatment all participants will discontinue treatment. Upon progression, participants can receive retreatment. | 125 |
| Nivolumab Monotherapy (Not Randomized) Participants receive nivolumab administered intravenously at 3 mg/kg every two weeks. Non-randomized participants were those participants who were enrolled but (after 1 year) were not randomized to either of the study cohorts (Cohort A or B). | 1,176 |
| Total | 1,428 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative reasons by sponsor | 8 | 5 | 0 |
| Overall Study | Adverse event unrelated to study drug | 6 | 4 | 45 |
| Overall Study | Death | 4 | 2 | 158 |
| Overall Study | Disease progression | 51 | 60 | 700 |
| Overall Study | Lost to Follow-up | 0 | 2 | 2 |
| Overall Study | Maximum clinical benefit | 2 | 2 | 3 |
| Overall Study | Other reasons | 16 | 15 | 50 |
| Overall Study | Participant no loner meets study criteria | 3 | 2 | 28 |
| Overall Study | Participant request to discontinue treatment | 12 | 12 | 70 |
| Overall Study | Participant withdrew consent | 10 | 18 | 61 |
| Overall Study | Poor/non-compliance | 2 | 1 | 1 |
| Overall Study | Study drug toxicity | 13 | 2 | 58 |
Baseline characteristics
| Characteristic | Cohort A: Nivolumab Monotherapy | Cohort B: Nivolumab Monotherapy | Nivolumab Monotherapy (Not Randomized) | Total |
|---|---|---|---|---|
| Age, Continuous | 66.2 Years STANDARD_DEVIATION 10.27 | 66.6 Years STANDARD_DEVIATION 7.97 | 66.1 Years STANDARD_DEVIATION 9.82 | 66.1 Years STANDARD_DEVIATION 9.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 31 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 124 Participants | 118 Participants | 1139 Participants | 1381 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 38 Participants | 42 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 8 Participants | 84 Participants | 105 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 | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 7 Participants | 8 Participants |
| Race (NIH/OMB) White | 111 Participants | 114 Participants | 1041 Participants | 1266 Participants |
| Sex: Female, Male Female | 67 Participants | 62 Participants | 528 Participants | 657 Participants |
| Sex: Female, Male Male | 60 Participants | 63 Participants | 648 Participants | 771 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 / 127 | 77 / 125 | 1,040 / 1,428 | 1,180 / 1,428 |
| other Total, other adverse events | 101 / 127 | 82 / 125 | 1,287 / 1,428 | 1,306 / 1,428 |
| serious Total, serious adverse events | 57 / 127 | 52 / 125 | 870 / 1,428 | 918 / 1,428 |
Outcome results
Primary
The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5)
A treatment related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that has a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Population: All treated participants prior to randomization and treated participants randomized to Cohort A and B
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Gastrointestinal Adverse Event (Grade3-4) | 3 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Skin Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Pulmonary Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Endocrinopathies (Grade3-4) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Skin Adverse Event (Grade3-4) | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Renal Adverse Event (Grade3-4) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hepatic Adverse Event (Grade3-4) | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Renal Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Endocrinopathies (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hypersensitivity/Infusion Reaction Events (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hepatic Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Gastrointestinal Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hypersensitivity/Infusion Reaction Events (Grade3-4) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Pulmonary Adverse Event (Grade3-4) | 1 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Gastrointestinal Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Gastrointestinal Adverse Event (Grade3-4) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Endocrinopathies (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hepatic Adverse Event (Grade3-4) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hepatic Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Pulmonary Adverse Event (Grade3-4) | 1 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Pulmonary Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Renal Adverse Event (Grade3-4) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Renal Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Skin Adverse Event (Grade3-4) | 1 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Skin Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hypersensitivity/Infusion Reaction Events (Grade3-4) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hypersensitivity/Infusion Reaction Events (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Endocrinopathies (Grade3-4) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Pulmonary Adverse Event (Grade3-4) | 18 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Endocrinopathies (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Skin Adverse Event (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hepatic Adverse Event (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Endocrinopathies (Grade3-4) | 6 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hypersensitivity/Infusion Reaction Events (Grade3-4) | 4 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hepatic Adverse Event (Grade3-4) | 19 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Gastrointestinal Adverse Event (Grade3-4) | 20 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Renal Adverse Event (Grade3-4) | 4 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Hypersensitivity/Infusion Reaction Events (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Renal Adverse Event (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Pulmonary Adverse Event (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Gastrointestinal Adverse Event (Grade 5) | 1 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) | Skin Adverse Event (Grade3-4) | 15 Participants |
Secondary
Median Time to Onset of Select Adverse Events (Grade 3-5)
The time from first dose to the first occurrence of any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Population: All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Endocrine Adverse Event | 12.14 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Gastrointestinal Adverse Event | 82.71 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Pulmonary Adverse Event | 156.21 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Hepatic Adverse Event | 84.50 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Renal Adverse Event | 108.00 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Skin Adverse Event | 26.14 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Hypersensitivity/Infusion Reaction | 42.00 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Endocrine Adverse Event | 25.3 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Skin Adverse Event | 18.14 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Renal Adverse Event | 15.1 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Gastrointestinal Adverse Event | 49.21 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Hypersensitivity/Infusion Reaction | 2.36 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Endocrine Adverse Event | 11.14 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Gastrointestinal Adverse Event | 17.86 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Hepatic Adverse Event | 4.14 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Pulmonary Adverse Event | 7.79 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Renal Adverse Event | 6.71 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Onset of Select Adverse Events (Grade 3-5) | Skin Adverse Event | 10.57 Weeks |
Secondary
Median Time to Resolution of Select Adverse Events (Grade 3-5)
The time from the onset of any select adverse event of interest to its resolution or stabilization. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Population: All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Endocrine Adverse Event | 3.43 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Gastrointestinal Adverse Event | 4.79 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Pulmonary Adverse Event | 1.14 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Hepatic Adverse Event | 1.36 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Renal Adverse Event | 0.64 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Skin Adverse Event | 2.57 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Hypersensitivity/Infusion Reaction | 0.1 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Endocrine Adverse Event | 1.00 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Skin Adverse Event | 2.43 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Renal Adverse Event | 1.9 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Gastrointestinal Adverse Event | 1.50 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Hypersensitivity/Infusion Reaction | 0.1 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Endocrine Adverse Event | 3.57 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Gastrointestinal Adverse Event | 1.86 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Hepatic Adverse Event | 12.57 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Pulmonary Adverse Event | 2.57 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Renal Adverse Event | 1.29 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | Median Time to Resolution of Select Adverse Events (Grade 3-5) | Skin Adverse Event | 9.14 Weeks |
Secondary
The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events
The number of participants receiving \> 40mg prednisone equivalents for any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Population: All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 3 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Renal Adverse Event | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Pulmonary Adverse Event | 7 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Endocrine Adverse Event | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 2 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Skin Adverse Event | 2 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Hepatic Adverse Event | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Pulmonary Adverse Event | 4 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Endocrine Adverse Event | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 2 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Hepatic Adverse Event | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Renal Adverse Event | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Skin Adverse Event | 2 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 1 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Renal Adverse Event | 10 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 21 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 3 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Skin Adverse Event | 14 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Pulmonary Adverse Event | 31 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Hepatic Adverse Event | 8 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events | Endocrine Adverse Event | 5 Participants |
Secondary
The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events
The number of participants receiving medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Population: All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Pulmonary Adverse Event | 11 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Hepatic Adverse Event | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Renal Adverse Event | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Endocrine Adverse Event | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Skin Adverse Event | 17 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 5 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 2 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Hepatic Adverse Event | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Pulmonary Adverse Event | 4 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Renal Adverse Event | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 1 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Endocrine Adverse Event | 2 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Skin Adverse Event | 8 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 2 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 35 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Endocrine Adverse Event | 15 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Pulmonary Adverse Event | 42 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 14 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Skin Adverse Event | 113 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Renal Adverse Event | 12 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events | Hepatic Adverse Event | 13 Participants |
Secondary
The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Population: All treated participants prior to randomization and treated participants randomized to Cohort A and B
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Gastrointestinal Adverse Event (Grade3-4) | 7 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Skin Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Pulmonary Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Endocrinopathies (Grade3-4) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Skin Adverse Event (Grade3-4) | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Renal Adverse Event (Grade3-4) | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Renal Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hepatic Adverse Event (Grade3-4) | 1 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Endocrinopathies (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hypersensitivity/Infusion Reaction Events (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hepatic Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Gastrointestinal Adverse Event (Grade 5) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hypersensitivity/Infusion Reaction Events (Grade3-4) | 0 Participants |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Pulmonary Adverse Event (Grade3-4) | 2 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hypersensitivity/Infusion Reaction Events (Grade3-4) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Gastrointestinal Adverse Event (Grade3-4) | 2 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Gastrointestinal Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hepatic Adverse Event (Grade3-4) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hepatic Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Pulmonary Adverse Event (Grade3-4) | 3 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Pulmonary Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Renal Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Skin Adverse Event (Grade3-4) | 2 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Skin Adverse Event (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Renal Adverse Event (Grade3-4) | 1 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hypersensitivity/Infusion Reaction Events (Grade 5) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Endocrinopathies (Grade3-4) | 0 Participants |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Endocrinopathies (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Endocrinopathies (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Skin Adverse Event (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hepatic Adverse Event (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Endocrinopathies (Grade3-4) | 8 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hypersensitivity/Infusion Reaction Events (Grade3-4) | 5 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hepatic Adverse Event (Grade3-4) | 34 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Gastrointestinal Adverse Event (Grade3-4) | 35 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Renal Adverse Event (Grade3-4) | 14 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Hypersensitivity/Infusion Reaction Events (Grade 5) | 0 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Renal Adverse Event (Grade 5) | 1 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Pulmonary Adverse Event (Grade 5) | 7 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Gastrointestinal Adverse Event (Grade 5) | 1 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Skin Adverse Event (Grade3-4) | 18 Participants |
| Nivolumab Monotherapy (Pre-Randomized) | The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events | Pulmonary Adverse Event (Grade3-4) | 31 Participants |
Secondary
The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events
The duration of time participants received medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
Time frame: From first dose first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months)
Population: All treated participants (both included and excluded from Cohort randomization) with at least one select adverse event from the category
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 5.43 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Renal Adverse Event | 0.7 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Pulmonary Adverse Event | 6.57 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Endocrine Adverse Event | NA Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 2.71 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Skin Adverse Event | 18.14 Weeks |
| Cohort A: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Hepatic Adverse Event | NA Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Pulmonary Adverse Event | 2.86 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Endocrine Adverse Event | 82.57 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 2.50 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Hepatic Adverse Event | NA Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Renal Adverse Event | NA Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Skin Adverse Event | 6.71 Weeks |
| Cohort B: Nivolumab Monotherapy (Post-Randomization) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 2.0 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Renal Adverse Event | 2.57 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Gastrointestinal Adverse Event | 3.79 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Hypersensitivity/Infusion Reaction | 0.14 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Skin Adverse Event | 4.07 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Pulmonary Adverse Event | 3.57 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Hepatic Adverse Event | 5.0 Weeks |
| Nivolumab Monotherapy (Pre-Randomized) | The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events | Endocrine Adverse Event | 2.57 Weeks |