Metastatic Renal Cell Carcinoma, Renal Cell Carcinoma
Conditions
Keywords
Kidney Cancer, Kidney Neoplasms, Renal Cancer, Renal Neoplasms, CD122, CD122-Biased Agonist, CD122-Biased Cytokine, IL-2 receptor agonist, Immuno-oncology therapy, NKTR-214, Nivolumab, Opdivo®, PD-L1, PD-1, Bempegaldesleukin, IL-2, BEMPEG, CD122-Preferential, IL-2 pathway agonist, Checkpoint inhibition, Immune checkpoint inhibitor
Brief summary
The main purpose of this study is to compare the objective response rate (ORR) and overall survival (OS) of bempegaldesleukin (NKTR-214: BEMPEG) combined with nivolumab to that of tyrosine kinase inhibitor (TKI) monotherapy (sunitinib or cabozantinib) in IMDC intermediate- or poor-risk patients and IMDC all-risk patients with previously untreated advanced renal cell carcinoma (RCC).
Interventions
BIOLOGICALbempegaldesleukin
Specified dose on specified days
DRUGsunitinib
Specified dose on specified days
BIOLOGICALnivolumab
Specified dose on specified days
DRUGcabozantinib
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Nektar Therapeutics
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
Key Inclusion Criteria: * Provide written, informed consent to participate in the study and follow the study procedures * Karnofsky Performance Status (KPS) of at least 70% * Measurable disease per mRECIST 1.1 criteria * Histologically confirmed RCC with a clear-cell component (may have sarcomatoid features); advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC * Patients with any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score (favorable-, intermediate-, or poor-risk) are eligible. At least one IMDC prognostic factor must be present to qualify as either intermediate- or poor-risk renal cell carcinoma. * No prior systemic therapy (including neoadjuvant, adjuvant, or vaccine therapy) for RCC Key
Exclusion criteria
* An active, known or suspected autoimmune disease that has required systemic treatment within the past 3 months (exceptions exist) * Patients who have a known additional malignancy that is progressing or requires active treatment (exceptions exist) * Any tumor invading the wall of a major blood vessels * Any tumor invading the gastrointestinal (GI) tract or any evidence of endotracheal or endobronchial tumor within 28 days prior to randomization * Need for \>2 medications for management of hypertension (including diuretics) * History of pulmonary embolism, deep vein thrombosis (not including tumor thrombus), or clinically significant thromboembolic event within 3 months of randomization Additional protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | Approximately 32 months | ORR using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1 by Blinded Independent Central Review (BICR) in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) All-risk patients and intermediate- or poor-risk patients. ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR. |
| Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC | Approximately 32 months | OS is defined as the time from date of first dose to the date of death from any cause. Patients without a date of death were censored at their last known alive date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | Approximately 32 months | Progression-free survival is defined as the time between the date of randomization and the first date of documented tumor progression using mRECIST 1.1 per BICR or death due to any cause, whichever comes first. |
Countries
Argentina, Australia, Brazil, Chile, Mexico, New Zealand, Peru, Russia, Singapore, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination of Bempegaldesleukin + Nivolumab Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.
Bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) every 3 weeks (q3w) combined with nivolumab 360 mg IV q3w | 311 |
| Sunitinib or Cabozantinib Patients in Arm B will receive the Investigator's choice of either one of two treatment options.
Sunitinib 50 mg per orally (po) once daily for 4 weeks followed by 2 weeks off OR Cabozantinib 60 mg po once daily | 312 |
| Total | 623 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Patient did not complete the end of study form but is not followed on the study anymore. | 1 | 0 |
| Overall Study | Withdrawal by Subject | 16 | 19 |
Baseline characteristics
| Characteristic | Combination of Bempegaldesleukin + Nivolumab | Sunitinib or Cabozantinib | Total |
|---|---|---|---|
| Age, Continuous | 61.5 Years STANDARD_DEVIATION 9.74 | 60.8 Years STANDARD_DEVIATION 10.24 | 61.2 Years STANDARD_DEVIATION 9.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 148 Participants | 131 Participants | 279 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 157 Participants | 172 Participants | 329 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 9 Participants | 15 Participants |
| Karnofsky Performance Status (KPS) Score KPS < 80 | 77 participants | 75 participants | 152 participants |
| Karnofsky Performance Status (KPS) Score KPS >= 80 | 234 participants | 237 participants | 471 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 14 Participants | 8 Participants | 22 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 6 Participants | 13 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 7 Participants | 8 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 11 Participants | 18 Participants |
| Race/Ethnicity, Customized White | 271 Participants | 272 Participants | 543 Participants |
| Region of Enrollment Argentina | 49 Participants | 28 Participants | 77 Participants |
| Region of Enrollment Australia | 7 Participants | 8 Participants | 15 Participants |
| Region of Enrollment Brazil | 68 Participants | 82 Participants | 150 Participants |
| Region of Enrollment Chile | 19 Participants | 16 Participants | 35 Participants |
| Region of Enrollment Mexico | 16 Participants | 11 Participants | 27 Participants |
| Region of Enrollment New Zealand | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Peru | 9 Participants | 5 Participants | 14 Participants |
| Region of Enrollment Russia | 95 Participants | 108 Participants | 203 Participants |
| Region of Enrollment Singapore | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 41 Participants | 50 Participants | 91 Participants |
| Sex: Female, Male Female | 75 Participants | 80 Participants | 155 Participants |
| Sex: Female, Male Male | 236 Participants | 232 Participants | 468 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 109 / 310 | 114 / 306 |
| other Total, other adverse events | 307 / 310 | 304 / 306 |
| serious Total, serious adverse events | 113 / 310 | 91 / 306 |
Outcome results
Primary
Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC
ORR using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1 by Blinded Independent Central Review (BICR) in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) All-risk patients and intermediate- or poor-risk patients. ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.
Time frame: Approximately 32 months
Population: A total of 623 patients randomized in the ITT All-risk population, including 514 patients for the ITT I/P-risk population:~* NKTR-214/nivolumab: 311 (ITT All-risk population) and 256 (ITT I/P-risk population), respectively~* Sunitinib or Cabozantinib (TKI): 312 (ITT All-risk population) and 258 (ITT I/P-risk population), respectively
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination of Bempegaldesleukin + Nivolumab | Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | ORR per mRECIST 1.1 by BICR, ITT All-risk population | 73 Participants |
| Combination of Bempegaldesleukin + Nivolumab | Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | ORR per mRECIST 1.1 by BICR, ITT I/P-risk population | 59 Participants |
| Sunitinib or Cabozantinib | Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | ORR per mRECIST 1.1 by BICR, ITT All-risk population | 109 Participants |
| Sunitinib or Cabozantinib | Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | ORR per mRECIST 1.1 by BICR, ITT I/P-risk population | 79 Participants |
Primary
Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC
OS is defined as the time from date of first dose to the date of death from any cause. Patients without a date of death were censored at their last known alive date.
Time frame: Approximately 32 months
Population: A total of 623 patients randomized in the ITT All-risk population, including 514 patients for the ITT I/P-risk population:~* NKTR-214/nivolumab: 311 (ITT All-risk population) and 256 (ITT I/P-risk population), respectively~* Sunitinib or Cabozantinib (TKI): 312 (ITT All-risk population) and 258 (ITT I/P-risk population), respectively
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combination of Bempegaldesleukin + Nivolumab | Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC | OS, ITT All-risk population | NA months |
| Combination of Bempegaldesleukin + Nivolumab | Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC | OS, ITT I/P-risk population | 29 months |
| Sunitinib or Cabozantinib | Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC | OS, ITT All-risk population | NA months |
| Sunitinib or Cabozantinib | Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC | OS, ITT I/P-risk population | NA months |
Secondary
Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC
Progression-free survival is defined as the time between the date of randomization and the first date of documented tumor progression using mRECIST 1.1 per BICR or death due to any cause, whichever comes first.
Time frame: Approximately 32 months
Population: A total of 623 patients randomized in the ITT All-risk population, including 514 patients for the ITT I/P-risk population:~* NKTR-214/nivolumab: 311 (ITT All-risk population) and 256 (ITT I/P-risk population), respectively~* Sunitinib or Cabozantinib (TKI): 312 (ITT All-risk population) and 258 (ITT I/P-risk population), respectively
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combination of Bempegaldesleukin + Nivolumab | Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | PFS per mRECIST 1.1. by BICR, ITT All-risk population | 8.2 Months |
| Combination of Bempegaldesleukin + Nivolumab | Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | PFS per mRECIST 1.1. by BICR, ITT I/P-risk population | 6.4 Months |
| Sunitinib or Cabozantinib | Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | PFS per mRECIST 1.1. by BICR, ITT All-risk population | 10.3 Months |
| Sunitinib or Cabozantinib | Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC | PFS per mRECIST 1.1. by BICR, ITT I/P-risk population | 9.2 Months |