A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma

• ClinicalTrials.gov Identifier: NCT03635983
• Recruitment Status: Active, not recruiting
• First Posted: August 17, 2018
• Last Update Posted: August 3, 2022
• Sponsor: Bristol-Myers Squibb
• Collaborator: Nektar Therapeutics
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: August 16, 2018
• First Posted Date: August 17, 2018
• Last Update Posted Date: August 3, 2022
• Actual Study Start Date: September 21, 2018
• Actual Primary Completion Date: November 19, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2018)

• Overall response rate (ORR) by Blinded Independent Central Review (BICR) [ Time Frame: Approximately 16 months ]
• Progression-free survival (PFS) by BICR [ Time Frame: Approximately 22 months ]
• Overall survival (OS) [ Time Frame: Up to 59 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 3, 2020)

• Clinical benefit rate (CBR) [ Time Frame: Approximately 16 months ]
• Duration of response (DoR) [ Time Frame: Approximately 16 months ]
• Time to response (TTR) [ Time Frame: Approximately 16 months ]
• ORR by investigator and in biomarker population [ Time Frame: Approximately 16 months ]
• PFS by investigator and in biomarker population [ Time Frame: Approximately 22 months ]
• OS in biomarker population [ Time Frame: Up to 59 months ]
• Incidence of participants with non-serious Adverse Events (AEs) [ Time Frame: Up to 5 years ]
• Incidence of participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 5 years ]
• Incidence of treatment-related AEs [ Time Frame: Up to 5 years ]
• Incidence of treatment-related SAEs [ Time Frame: Up to 5 years ]
• Incidence of laboratory abnormalities in blood [ Time Frame: Up to 5 years ]
• Incidence of laboratory abnormalities in blood serum [ Time Frame: Up to 5 years ]
• Incidence of laboratory abnormalities in urine [ Time Frame: Up to 5 years ]

Original Secondary Outcome Measures (submitted: August 16, 2018)

• Clinical benefit rate (CBR) [ Time Frame: Approximately 16 months ]
• Duration of response (DoR) [ Time Frame: Approximately 16 months ]
• Duration of overall complete response (DoCR) [ Time Frame: Approximately 16 months ]
• Time to response (TTR) [ Time Frame: Approximately 16 months ]
• ORR by investigator and in biomarker population [ Time Frame: Approximately 16 months ]
• PFS by investigator and in biomarker population [ Time Frame: Approximately 22 months ]
• OS in biomarker population [ Time Frame: Up to 59 months ]
• Incidence of participants with non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) leading to discontinuation [ Time Frame: Up to 5 years ]
• Incidence of treatment-related AEs [ Time Frame: Up to 5 years ]
• Incidence of treatment-related SAEs [ Time Frame: Up to 5 years ]
• Incidence of laboratory abnormalities [ Time Frame: Up to 5 years ]

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

Descriptive Information

• Brief Title: A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma
• Official Title: A Phase 3, Randomized, Open-label Study of NKTR-214 Combined With Nivolumab Versus Nivolumab in Participants With Previously Untreated Unresectable or Metastatic Melanoma
• Brief Summary: The purpose of the study is to test the effectiveness (how well the drug works), safety, and tolerability of the investigational drug called NKTR-214, when combined with nivolumab versus nivolumab given alone in participants with previously untreated melanoma skin cancer that is either unable to be surgically removed or has spread
• 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: Melanoma

Intervention

• Biological: NKTR-214
  Specified dose on specified days
  Other Names:

  • Bempegaldesleukin
  • BMS-986321
• Biological: Nivolumab
  Specified dose on specified days
  Other Names:

  • Opdivo
  • BMS-936558

Study Arms

• Experimental: Combination
  NKTR-214 + Nivolumab
  Interventions:

  • Biological: NKTR-214
  • Biological: Nivolumab
• Experimental: Monotherapy
  Nivolumab
  Intervention: Biological: Nivolumab

• Publications *: Khushalani NI, Diab A, Ascierto PA, Larkin J, Sandhu S, Sznol M, Koon HB, Jarkowski A, Zhou M, Statkevich P, Geese WJ, Long GV. Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. Future Oncol. 2020 Oct;16(28):2165-2175. doi: 10.2217/fon-2020-0351. Epub 2020 Jul 29.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 17, 2022): 783
• Original Estimated Enrollment (submitted: August 16, 2018): 764
• Estimated Study Completion Date: February 28, 2024
• Actual Primary Completion Date: November 19, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 (adults 18 years or older)/Lansky Performance Score ≥ 80% (minors ages 12-17 only)
• Histologically confirmed stage III (unresectable) or stage IV melanoma
• Treatment-naive participants (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma) with the exception of prior adjuvant and/or neoadjuvant treatment for melanoma with approved agents

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases
• Uveal melanoma
• Participants with an active, known or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Finland, France, Germany, Greece, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT03635983
• Other Study ID Numbers: CA045-001; 2018-001423-40 ( EudraCT Number ); 17-214-08 ( Other Identifier: Nektar Therapeutics )
• 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: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Nektar Therapeutics

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: August 2022