Renal Cell Carcinoma
Conditions
Keywords
Advanced/Metastatic, clear cell component
Brief summary
The purpose of this study is to measure how active BMS-936558 (nivolumab) is against Renal Cell Carcinoma (RCC) as measured by the disease not progressing and whether a dose response relationship exists.
Interventions
BIOLOGICALnivolumab
Solution, Intravenous (IV), 0.3 mg/kg, every 3 weeks (Q 3 weeks), Until Progressive disease (PD), toxicity or discontinue for other reasons
Sponsors
Ono Pharma USA Inc
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic confirmation of Renal cell carcinoma (RCC) with a clear cell component * Previous treatment with at least one anti-angiogenic agent * Progressed within 6 months of study enrollment * Subjects should not have had more than 3 prior treatments for locally advanced or metastatic disease * Must have available tumor tissue for submission * Subjects must also meet various laboratory parameters for inclusion
Exclusion criteria
* Subjects with any active autoimmune disease or a history of known autoimmune disease Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization to disease progression or death (up to approximately 2 years) | PFS is defined as the time from randomization to date of first disease progression (either clinical or radiographic progression, as assessed by the investigator). Tumor assessments (radiographic scans) were done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression. Survival was assessed every 3 months. The analysis of PFS was conducted after approximately 116 events (progression or death), approximately 2 years. PFS was calculated based on investigator's assessment of first date of progression (either clinical or radiographic progression) or date of death if progression did not occur. Progression was at least a 20% increase in the sum of diameters of the longest target lesions since screening (the sum must be an absolute increase of at least 5 mm), or measurable increase in non-target lesion or appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (BORR) | From randomization until disease progression or discontinuation of study therapy (up to approximately 2 years) | BORR is defined as the percentage of participants whose best response is either partial response (PR) or complete response (CR). Tumor response was evaluated by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 80% confidence interval is based on the Clopper and Pearson method |
| Overall Survival (OS) | From randomization to to date of death (up to approximately 8 years) | OS is defined as the time from date of randomization until date of death. If the participant did not die, overall survival will be censored on the last date the participant was known to be alive. Survival status is collected at each visit during treatment and every 3 months during follow-up. OS is based on Kaplan-Meier estimates. |
| Number of Participants Experiencing Adverse Events | From first dose to 30 days following last dose (up to approximately 6 years) | Number of participants experiencing different types of events, including Adverse Events (AEs), Drug-related AEs, AEs leading to discontinuation, Drug-related AEs leading to discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs. Events are classified based on the NCI Common Terminology Criteria (CTC) version 4.0 |
Countries
Canada, Finland, Italy, United States
Participant flow
Pre-assignment details
168 participants were randomized, 167 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab 0.3 mg/kg Nivolumab 0.3 mg/kg IV Q3W | 60 |
| Nivolumab 2 mg/kg Nivolumab 2 mg/kg IV Q3W | 54 |
| Nivolumab 10 mg/kg Nivolumab 10 mg/kg IV Q3W | 54 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Pre-Treatment Period | Not reported | 1 | 0 | 0 |
| Treatment Period | AE unrelated to study drug | 1 | 2 | 5 |
| Treatment Period | Death | 0 | 1 | 0 |
| Treatment Period | Disease Progression | 50 | 40 | 44 |
| Treatment Period | Participant no longer meeting study criteria | 1 | 0 | 0 |
| Treatment Period | Participant request to discontinue | 2 | 2 | 1 |
| Treatment Period | Participant withdrew consent | 0 | 1 | 0 |
| Treatment Period | Study Drug Toxicity | 5 | 8 | 4 |
Baseline characteristics
| Characteristic | Nivolumab 0.3 mg/kg | Nivolumab 2 mg/kg | Nivolumab 10 mg/kg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 13 Participants | 19 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 41 Participants | 35 Participants | 113 Participants |
| Age, Continuous | 61.0 years STANDARD_DEVIATION 8.8 | 60.8 years STANDARD_DEVIATION 8.2 | 60.6 years STANDARD_DEVIATION 9.6 | 60.8 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 53 Participants | 54 Participants | 160 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 1 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Female | 19 Participants | 14 Participants | 14 Participants | 47 Participants |
| Sex: Female, Male Male | 41 Participants | 40 Participants | 40 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 51 / 60 | 46 / 54 | 47 / 54 |
| other Total, other adverse events | 55 / 59 | 54 / 54 | 52 / 54 |
| serious Total, serious adverse events | 30 / 59 | 35 / 54 | 24 / 54 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is defined as the time from randomization to date of first disease progression (either clinical or radiographic progression, as assessed by the investigator). Tumor assessments (radiographic scans) were done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression. Survival was assessed every 3 months. The analysis of PFS was conducted after approximately 116 events (progression or death), approximately 2 years. PFS was calculated based on investigator's assessment of first date of progression (either clinical or radiographic progression) or date of death if progression did not occur. Progression was at least a 20% increase in the sum of diameters of the longest target lesions since screening (the sum must be an absolute increase of at least 5 mm), or measurable increase in non-target lesion or appearance of one or more new lesions.
Time frame: From randomization to disease progression or death (up to approximately 2 years)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 0.3 mg/kg | Progression Free Survival (PFS) | 2.63 Months |
| Nivolumab 2 mg/kg | Progression Free Survival (PFS) | 4.11 Months |
| Nivolumab 10 mg/kg | Progression Free Survival (PFS) | 4.17 Months |
Secondary
Best Overall Response Rate (BORR)
BORR is defined as the percentage of participants whose best response is either partial response (PR) or complete response (CR). Tumor response was evaluated by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 80% confidence interval is based on the Clopper and Pearson method
Time frame: From randomization until disease progression or discontinuation of study therapy (up to approximately 2 years)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab 0.3 mg/kg | Best Overall Response Rate (BORR) | 20.0 Percent of participants |
| Nivolumab 2 mg/kg | Best Overall Response Rate (BORR) | 24.1 Percent of participants |
| Nivolumab 10 mg/kg | Best Overall Response Rate (BORR) | 20.4 Percent of participants |
Secondary
Number of Participants Experiencing Adverse Events
Number of participants experiencing different types of events, including Adverse Events (AEs), Drug-related AEs, AEs leading to discontinuation, Drug-related AEs leading to discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs. Events are classified based on the NCI Common Terminology Criteria (CTC) version 4.0
Time frame: From first dose to 30 days following last dose (up to approximately 6 years)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nivolumab 0.3 mg/kg | Number of Participants Experiencing Adverse Events | Any AEs | 58 Participants |
| Nivolumab 0.3 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related AEs | 44 Participants |
| Nivolumab 0.3 mg/kg | Number of Participants Experiencing Adverse Events | AEs leading to discontinuation | 6 Participants |
| Nivolumab 0.3 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related AEs leading to discontinuation | 4 Participants |
| Nivolumab 0.3 mg/kg | Number of Participants Experiencing Adverse Events | SAEs | 26 Participants |
| Nivolumab 0.3 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related SAEs | 3 Participants |
| Nivolumab 2 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related SAEs | 4 Participants |
| Nivolumab 2 mg/kg | Number of Participants Experiencing Adverse Events | Any AEs | 54 Participants |
| Nivolumab 2 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related AEs leading to discontinuation | 5 Participants |
| Nivolumab 2 mg/kg | Number of Participants Experiencing Adverse Events | SAEs | 26 Participants |
| Nivolumab 2 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related AEs | 36 Participants |
| Nivolumab 2 mg/kg | Number of Participants Experiencing Adverse Events | AEs leading to discontinuation | 10 Participants |
| Nivolumab 10 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related AEs | 41 Participants |
| Nivolumab 10 mg/kg | Number of Participants Experiencing Adverse Events | AEs leading to discontinuation | 10 Participants |
| Nivolumab 10 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related SAEs | 3 Participants |
| Nivolumab 10 mg/kg | Number of Participants Experiencing Adverse Events | Drug-related AEs leading to discontinuation | 4 Participants |
| Nivolumab 10 mg/kg | Number of Participants Experiencing Adverse Events | Any AEs | 53 Participants |
| Nivolumab 10 mg/kg | Number of Participants Experiencing Adverse Events | SAEs | 22 Participants |
Secondary
Overall Survival (OS)
OS is defined as the time from date of randomization until date of death. If the participant did not die, overall survival will be censored on the last date the participant was known to be alive. Survival status is collected at each visit during treatment and every 3 months during follow-up. OS is based on Kaplan-Meier estimates.
Time frame: From randomization to to date of death (up to approximately 8 years)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab 0.3 mg/kg | Overall Survival (OS) | 18.45 Months |
| Nivolumab 2 mg/kg | Overall Survival (OS) | 25.46 Months |
| Nivolumab 10 mg/kg | Overall Survival (OS) | 24.82 Months |