A Phase 3 Randomized Open Label Study to Compare NKTR-214 Combined With Nivolumab to the Investigator's Choice of Sunitinib or Cabozantinib in Patients With Previously Untreated Advanced Renal Cell Carcinoma
Overview
- Phase
- Phase 3
- Intervention
- bempegaldesleukin
- Conditions
- Renal Cell Carcinoma
- Sponsor
- Nektar Therapeutics
- Enrollment
- 623
- Locations
- 95
- Primary Endpoint
- Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
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).
Investigators
Eligibility Criteria
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
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/exclusion criteria and exceptions apply
Arms & Interventions
Combination of bempegaldesleukin + nivolumab
Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.
Intervention: bempegaldesleukin
Combination of bempegaldesleukin + nivolumab
Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.
Intervention: nivolumab
sunitinib or cabozantinib
Patients in Arm B will receive the Investigator's choice of either one of two treatment options.
Intervention: sunitinib
sunitinib or cabozantinib
Patients in Arm B will receive the Investigator's choice of either one of two treatment options.
Intervention: cabozantinib
Outcomes
Primary Outcomes
Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC
Time Frame: 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.
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
Time Frame: 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.
Secondary Outcomes
- 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)