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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)

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

Tracking Information
First Submitted Date  ICMJE October 29, 2018
First Posted Date  ICMJE November 2, 2018
Last Update Posted Date April 4, 2022
Actual Study Start Date  ICMJE December 18, 2018
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Cell Carcinoma
  • Metastatic Renal Cell Carcinoma
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 3, 2021)
623
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2018)
600
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Chile,   Hong Kong,   Mexico,   New Zealand,   Peru,   Russian Federation,   Singapore,   United States
Removed Location Countries China,   Colombia
 
Administrative Information
NCT Number  ICMJE NCT03729245
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Nektar Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Nektar Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Study Director Nektar Therapeutics
PRS Account Nektar Therapeutics
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP