A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)

• ClinicalTrials.gov Identifier: NCT03729245
• Recruitment Status: Active, not recruiting
• First Posted: November 2, 2018
• Last Update Posted: April 4, 2022
• Sponsor: Nektar Therapeutics
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Nektar Therapeutics

Tracking Information

• First Submitted Date: October 29, 2018
• First Posted Date: November 2, 2018
• Last Update Posted Date: April 4, 2022
• Actual Study Start Date: December 18, 2018
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2021)

• ORR using mRECIST 1.1 by BICR in IMDC intermediate- or poor-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) intermediate- or poor-risk patients. ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or 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.
• ORR per mRECIST 1.1 by BICR in IMDC all-risk patients with previously untreated advanced RCC [ Time Frame: Approximately 32 months ]
  ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or 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 intermediate- or poor-risk patients with previously untreated advanced RCC [ Time Frame: 32-59 months ]
  OS is defined as the time from date of first dose to the date of death.
• OS in IMDC all-risk patients with previously untreated advanced RCC [ Time Frame: 32-59 months ]
  OS is defined as the time from date of first dose to the date of death.

Original Primary Outcome Measures (submitted: October 31, 2018)

• Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Approximately 2 years ]
• Overall survival (OS) [ Time Frame: 27-48 months ]

Current Secondary Outcome Measures (submitted: November 23, 2021)

• Progression-free survival (PFS) per mRECIST 1.1 by BICR in IMDC intermediate- or poor-risk patients with previously untreated advanced RCC [ Time Frame: 32-59 months ]
  PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause.
• PFS per mRECIST 1.1 by BICR in IMDC all risk-patients with previously untreated advanced RCC [ Time Frame: 32-59 months ]
  PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause.
• Incidence of treatment-related Adverse Events (AEs) of Bempegaldesleukin combined with Nivolumab versus TKI monotherapy (sunitinib or cabozantinib) in patients with previously untreated advanced RCC [ Time Frame: Up to 5 years ]
• Changes in cancer-related symptoms and quality-of-life in patients using the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN/FACT) Symptom Index for Kidney Cancer (FKSI-19) [ Time Frame: 32-59 months ]
  Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-P domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to 12 questions ("I have a lack of energy," "I feel pain," for example) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 48). A negative change from baseline indicates a worsening of condition.
• PD-L1 expression on tumor cells (< 1% vs ≥ 1%) using the PD-L1 immunohistochemistry (IHC) 28-8 pharmDx assay as a predictive biomarker for ORR, PFS, and OS in patients with previously untreated advanced RCC [ Time Frame: 32-59 months ]

Original Secondary Outcome Measures (submitted: October 31, 2018)

• Progression-free survival (PFS) by BICR [ Time Frame: 27-48 months ]
• Incidence of treatment-related Adverse Events (AEs) [ Time Frame: Up to 5 years ]
• ORR using RECIST 1.1 by investigator and in biomarker population [ Time Frame: 27-48 months ]
• PFS by investigator and in biomarker population [ Time Frame: 27-48 months ]
• OS in biomarker population [ Time Frame: 27-48 months ]
• Changes in cancer-related symptoms and quality-of-life in patients using the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN/FACT) Symptom Index for Kidney Cancer (FKSI-19) [ Time Frame: 27-48 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)
• Official Title: 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Renal Cell Carcinoma
• Metastatic Renal Cell Carcinoma

Intervention

• Biological: bempegaldesleukin
  Specified dose on specified days
  Other Names:

  • BEMPEG
  • BMS-986321
• Drug: sunitinib
  Specified dose on specified days
  Other Name: Sutent®
• Biological: nivolumab
  Specified dose on specified days
  Other Names:

  • Opdivo®
  • BMS-936558
• Drug: cabozantinib
  Specified dose on specified days
  Other Name: Cabometyx®

Study Arms

• Experimental: Combination of bempegaldesleukin + nivolumab
  Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.
  Interventions:

  • Biological: bempegaldesleukin
  • Biological: nivolumab
• Active Comparator: sunitinib or cabozantinib
  Patients in Arm B will receive the Investigator's choice of either one of two treatment options.
  Interventions:

  • Drug: sunitinib
  • Drug: cabozantinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 3, 2021): 623
• Original Estimated Enrollment (submitted: October 31, 2018): 600
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Eligibility 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/exclusion criteria and exceptions apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Chile, Hong Kong, Mexico, New Zealand, Peru, Russian Federation, Singapore, United States
• Removed Location Countries: China, Colombia

Administrative Information

• NCT Number: NCT03729245
• Other Study ID Numbers: 17-214-09; CA045002 ( Other Identifier: Bristol-Myers Squibb Protocol ID )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Nektar Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Nektar Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

• Study Director: Study Director; Nektar Therapeutics

• PRS Account: Nektar Therapeutics
• Verification Date: March 2022