PIVOT IO 020: A Study of Bempegaldesleukin (BEMPEG: NKTR-214) in Combination With Nivolumab in Children, Adolescents and Young Adults With Recurrent or Treatment-resistant Cancer

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT04730349
Collaborator
Nektar Therapeutics (Industry)
15
18
13
12.6
0.8
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to first, in Part A, assess the safety, tolerability and drug levels of Bempegaldesleukin (BEMPEG) in combination with nivolumab and then, in Part B, to estimate the preliminary efficacy in children, adolescents and young adults with recurrent or treatment-resistant cancer.

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2 Study of Bempegaldesleukin in Combination With Nivolumab in Children, Adolescents, and Young Adults With Recurrent or Refractory Malignancies (PIVOT IO 020)
Actual Study Start Date :
Jun 3, 2021
Actual Primary Completion Date :
Jun 22, 2022
Actual Study Completion Date :
Jun 22, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: A1W Dosing schema

Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: A1F Dosing schema

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: A2W Dosing schema

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: A2F Dosing schema

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B1 Neuroblastoma

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B2 Ewing sarcoma

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B3 Rhabdomyosarcoma

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B4 Miscellaneous solid tumors

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B5 NHL/leukemia

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B6 High-grade glioma

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B7 Medulloblastoma and Embryonal Tumors

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B8 Ependymoma

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Experimental: Part B: Cohort B9 Miscellaneous brain tumors

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • BMS-936558-01
  • Biological: NKTR-214
    Specified dose on specified days
    Other Names:
  • Bempegaldesleukin (BEMPEG)
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of dose-limiting toxicities [Up to 2 years and 100 days]

      Part A

    2. Incidence of adverse events (AEs) [Up to 2 years and 100 days]

      Part A

    3. Incidence of serious AEs (SAEs) [Up to 2 years and 100 days]

      Part A

    4. Incidence of drug-related AEs [Up to 2 years and 100 days]

      Part A

    5. Incidence of AEs leading to discontinuation [Up to 2 years and 100 days]

      Part A

    6. Incidence of death [Up to 2 years and 100 days]

      Part A

    7. Pharmacokinetic (PK) parameters: Peak concentration [Up to 2 years]

      Part A

    8. Pharmacokinetic (PK) parameters: Trough concentration [Up to 2 years]

      Part A

    9. Pharmacokinetic (PK) parameters: Time-averaged concentration [Up to 2 years]

      Part A

    10. Pharmacokinetic (PK) parameters: Clearance (CL) [Up to 2 years]

      Part A

    11. Pharmacokinetic (PK) parameters: Volume of distribution (Vd) [Up to 2 years]

      Part A

    12. Investigator-assessed objective response rate (ORR) [Up to 5 years]

      Part B

    Secondary Outcome Measures

    1. Incidence of AEs [Up to 5 years]

      Part B

    2. Incidence of SAEs [Up to 5 years]

      Part B

    3. Incidence of drug-related AEs [Up to 5 years]

      Part B

    4. Incidence of AEs leading to discontinuation [Up to 5 years]

      Part B

    5. Incidence of death [Up to 5 years]

      Part B

    6. Incidence of laboratory abnormalities: Hematology tests [Up to 5 years]

      Part B

    7. Incidence of laboratory abnormalities: Clinical chemistry tests [Up to 5 years]

      Part B

    8. Progression-free survival (PFS) [Up to 5 years]

      Part B

    9. Overall survival (OS) [Up to 5 years]

      Part B

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age < 18 years for Part A and Part B

    • Age up to 30 years for Part B Cohorts B2, B3 and B4

    • Must have received standard of care therapy and there must be no potentially curative treatment available

    • Histologically confirmed with malignant neoplasms that are refractory, relapsed, or curative treatments are lacking

    • Must have measurable or evaluable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for solid tumors, Response Assessment in Neuro-Oncology (RANO) or Response Assessment in Pediatric Neuro-Oncology (RAPNO) for central nervous system tumors, International Pediatric Non-Hodgkin Lymphoma Response Criteria for non-Hodgkin lymphoma (NHL), revised International Neuroblastoma Response Criteria (INRC) for neuroblastoma, modified National Comprehensive Cancer Network (NCCN) Criteria for acute lymphoblastic leukemia, and modified Cheson et al International Working Group criteria for acute myeloid leukemia

    • Lansky play score for age ≤ 16 years or Karnofsky performance score for age > 16 years assessed within 2 weeks of enrollment must be ≥ 60

    Exclusion Criteria:
    • Osteosarcoma, T-cell/Natural Killer (NK) cell leukemia/lymphoma, and Hodgkin's lymphoma

    • Need for > 2 antihypertensive medications for management of hypertension (including diuretics)

    • Known cardiovascular history, including unstable or deteriorating cardiac disease, within the previous 12 months prior to screening

    • Inadequately treated adrenal insufficiency

    • Active, known, or suspected autoimmune disease

    • Active infection requiring systemic therapy within 14 days prior to first dose

    • Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment

    • Prior allogeneic stem cell transplant

    • Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either suspected or confirmed within 4 weeks prior to screening

    Other protocol-defined inclusion/exclusion criteria apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Local Institution - 0029 Little Rock Arkansas United States 72202
    2 Local Institution - 0011 Saint Louis Missouri United States 63110
    3 Local Institution - 0001 Randwick New South Wales Australia 2031
    4 Local Institution South Brisbane Queensland Australia 4101
    5 Local Institution - 0002 Parkville Victoria Australia 3052
    6 Local Institution - 0003 Perth Western Australia Australia 6009
    7 Local Institution - 0013 Villejuif Val-de-Marne France 94805
    8 Local Institution - 0014 Lyon France 69373 cedex 03
    9 Local Institution - 0016 Marseille France 13385
    10 Local Institution - 0015 Paris France 75005
    11 Local Institution - 0038 Hamburg Germany 20246
    12 Local Institution - 0039 Tuebingen Germany 72076
    13 Local Institution - 0037 Wuerzburg Germany 97080
    14 Local Institution - 0027 Milan Italy 20133
    15 Local Institution - 0008 Barcelona Spain 08035
    16 Local Institution - 0009 Madrid Spain 28009
    17 Local Institution - 0059 Sevilla Spain 41013
    18 Local Institution - 0028 València Spain 46026

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • Nektar Therapeutics

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT04730349
    Other Study ID Numbers:
    • CA045-020
    • 2020-000854-85
    First Posted:
    Jan 29, 2021
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022

    Study Results

    No Results Posted as of Aug 1, 2022