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)

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

Tracking Information

• First Submitted Date: May 27, 2020
• First Posted Date: June 1, 2020
• Last Update Posted Date: August 26, 2020
• Actual Study Start Date: July 27, 2020
• Estimated Primary Completion Date: July 2027 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: 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: 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: Interventional
• Study Phase: Phase 3

Study Design

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

• Melanoma
• Melanoma Stage III
• Melanoma Stage IV
• Melanoma (Skin)

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 27, 2020): 950
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: July 2027 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04410445
• Other Study ID Numbers: 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

• Plan to Share IPD: Undecided

• Responsible Party: Nektar Therapeutics
• Study Sponsor: Nektar Therapeutics
• Collaborators: Bristol-Myers Squibb

Investigators

• Study Director: Mann Muhsin, MD; Nektar Therapeutics

• PRS Account: Nektar Therapeutics
• Verification Date: August 2020