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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

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.

Condition or disease Intervention/treatment Phase
Melanoma Melanoma Stage III Melanoma Stage IV Melanoma (Skin) Biological: Bempegaldesleukin Biological: Nivolumab Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 950 participants
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
Official Title: 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)
Actual Study Start Date : July 27, 2020
Estimated Primary Completion Date : July 2027
Estimated Study Completion Date : July 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Nivolumab

Arm Intervention/treatment
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.
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

Active Comparator: Nivolumab
Arm B: Participants will receive nivolumab 480mg IV alone every 4 weeks.
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo®
  • BMS-936558




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04410445


Contacts
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Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com

Locations
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United States, California
Investigator Site - Whittier Recruiting
Whittier, California, United States, 90603
United States, Nebraska
Investigator Site - Omaha Recruiting
Omaha, Nebraska, United States, 68114
United States, Tennessee
Investigator Site - Knoxville Recruiting
Knoxville, Tennessee, United States, 37920
Sponsors and Collaborators
Nektar Therapeutics
Bristol-Myers Squibb
Investigators
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Study Director: Mann Muhsin, MD Nektar Therapeutics
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Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT04410445    
Other Study ID Numbers: 20-214-29/CA045-022
First Posted: June 1, 2020    Key Record Dates
Last Update Posted: August 26, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nektar Therapeutics:
CD122-Biased Agonist
CD122-Biased Cytokine
IL-2 Receptor Agonist
NKTR-214
Bempegaldesleukin
IL-2
Immunotherapy
BEMPEG
Nivolumab
Opdivo®
NIVO
Adjuvant
Skin Cancer
Resectable Melanoma
High Risk of Recurrence Melanoma
Post Resection
Checkpoint Inhibitor
Additional relevant MeSH terms:
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Melanoma
Recurrence
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Disease Attributes
Pathologic Processes
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents