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Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence (PIVOT-12)

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ClinicalTrials.gov Identifier: NCT04410445
Recruitment Status : Recruiting
First Posted : June 1, 2020
Last Update Posted : August 26, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Nektar Therapeutics

Tracking Information
First Submitted Date  ICMJE May 27, 2020
First Posted Date  ICMJE June 1, 2020
Last Update Posted Date August 26, 2020
Actual Study Start Date  ICMJE July 27, 2020
Estimated Primary Completion Date July 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2020)
RFS of bempegaldesleukin plus nivolumab versus nivolumab alone by BICR, is defined as the time between date of randomization and date of first recurrence, new primary melanoma, or all-cause death [ Time Frame: Approximately up to 60 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 27, 2020)
To compare the efficacy, as measured by RFS by BICR, of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA), Stage IIIB/C/D, or Stage IV cutaneous melanoma with NED who are at high risk for recurrence [ Time Frame: Approximately up to 60 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2020)
  • Overall Survival (OS) defined as the time between the date of randomization and the date of death due to any cause [ Time Frame: Approximately up to 83 months ]
  • Distant Metastasis Free Survival is defined as the time between the date of randomization and the date of first distant metastasis or date of death due to any cause, whichever occurs first, will be evaluated in patients who are Stage III at study entry [ Time Frame: Approximately up to 60 months ]
  • Overall safety and tolerability of bempegaldesleukin plus nivolumab will be measured by the incidence of AEs, SAEs, deaths, and laboratory abnormalities using CTCAE Version 5.0 criteria [ Time Frame: Approximately up to 60 months ]
  • Patient Reported Outcomes will be measured by changes from baseline in scores for the global health/quality of life and physical functioning subscales of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire [ Time Frame: Approximately up to 60 months ]
  • The predictive strength of PD-L1 expression as a biomarker will be measured by the endpoint RFS by BICR based on PD-L1 expression level [ Time Frame: Approximately up to 60 months ]
  • RFS by Investigator will be measured similarly to the primary endpoint, but recurrence and new primary melanoma will be decided by the Investigator [ Time Frame: Approximately up to 60 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2020)
  • To compare the overall survival (OS) of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (LN metastasis> 1 mm), Stage IIIB/C/D, or Stage IV NED melanoma [ Time Frame: Approximately up to 83 months ]
  • To evaluate distant metastasis-free survival (DMFS) by Investigator in patients who have Stage IIIA (LN metastasis > 1 mm) or IIIB/C/D melanoma at study entry [ Time Frame: Approximately up to 60 months ]
  • To assess the overall safety and tolerability of bempegaldesleukin plus nivolumab versus nivolumab in study patients [ Time Frame: Approximately up to 60 months ]
  • To describe changes in patient-reported outcomes as assessed by the global health/quality of life (GH/QoL) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Approximately up to 60 months ]
  • To evaluate the association between programmed cell death ligand 1 (PD-L1) expression status and RFS by BICR [ Time Frame: Approximately up to 60 months ]
  • To assess the efficacy, as measured by RFS by Investigator, of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (LN metastasis > 1 mm), Stage IIIB/C/D, or Stage IV NED melanoma [ Time Frame: Approximately up to 60 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence
Official Title  ICMJE A Phase 3, Randomized, Open-label Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence (PIVOT-12)
Brief Summary The main purpose of this study is to compare the efficacy of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA/B/C/D, or Stage IV cutaneous melanoma who are at high risk for recurrence.
Detailed Description The main purpose of this study is to compare the efficacy, as measured by recurrence-free survival (RFS) by blinded independent central review (BICR), of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (lymph node [LN] metastasis > 1 mm), Stage IIIB/C/D, or Stage IV (American Joint Committee on Cancer [AJCC] 8th edition) cutaneous melanoma with no evidence of disease (NED) who are at high risk for recurrence.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients will be randomized in a 1:1 ratio to one of two treatment arms
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma
  • Melanoma Stage III
  • Melanoma Stage IV
  • Melanoma (Skin)
Intervention  ICMJE
  • Biological: Bempegaldesleukin
    Specified dose on specified days
    Other Names:
    • NKTR-214
    • BMS-986321
  • Biological: Nivolumab
    Specified dose on specified days
    Other Names:
    • Opdivo®
    • BMS-936558
Study Arms  ICMJE
  • Experimental: Combination of bempegaldesleukin (NKTR-214) + nivolumab
    Arm A: Participants will receive bempegaldesleukin (NKTR-214) 0.006mg/kg IV in combination with nivolumab 360mg every 3 weeks.
    Interventions:
    • Biological: Bempegaldesleukin
    • Biological: Nivolumab
  • Active Comparator: Nivolumab
    Arm B: Participants will receive nivolumab 480mg IV alone every 4 weeks.
    Intervention: Biological: Nivolumab
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 27, 2020)
950
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2027
Estimated Primary Completion Date July 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients, age 12 years or older at the time of signing the informed consent form (age 18 years or older where local regulations or institutional policies do not allow for patients < 18 years of age to participate).
  • Histologically confirmed Stage IIIA (LN metastasis > 1 mm), IIIB/C/D, or IV (M1a/b/c/d) cutaneous melanoma by AJCC (8th edition) at study entry that has been completely surgically resected within 12 weeks prior to randomization.
  • Tumor tissue from biopsy or resected disease must be provided to central laboratory for PD-L1 status analysis. Must have PD-L1 expression classification for stratification purposes.
  • Disease-free status documented by a complete physical examination and imaging studies within 28 days prior to randomization.

Exclusion Criteria:

  • History of ocular/uveal melanoma or mucosal melanoma.
  • Active, known or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy for central nervous system lesions.
  • Prior therapy with interferon, talimogene laherparepvec (Imylgic®), interleukin-2 (IL-2) directed therapy, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte-associated protein 4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways).
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04410445
Other Study ID Numbers  ICMJE 20-214-29/CA045-022
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
Responsible Party Nektar Therapeutics
Study Sponsor  ICMJE Nektar Therapeutics
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Mann Muhsin, MD Nektar Therapeutics
PRS Account Nektar Therapeutics
Verification Date August 2020

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