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

Phase 1/2 Study of Bempegaldesleukin in Combination With Nivolumab in Children, Adolescents, and Young Adults With Recurrent or Refractory Malignancies (PIVOT IO 020)

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 Overview

• Status: Terminated
• Conditions: Ewing Sarcoma; Ependymoma; Medulloblastoma; Neuroblastoma; Rhabdomyosarcoma; High-grade Glioma; Leukemia and Lymphoma; Miscellaneous Brain Tumors; Miscellaneous Solid Tumors; Relapsed, Refractory Malignant Neoplasms
• Intervention / Treatment: Biological: Nivolumab; Biological: NKTR-214

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Local Institution - 0001
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Local Institution
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Local Institution - 0002
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Local Institution - 0003
• France
  • Lyon, France, 69373 cedex 03
    • Local Institution - 0014
  • Marseille, France, 13385
    • Local Institution - 0016
  • Paris, France, 75005
    • Local Institution - 0015
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Local Institution - 0013
• Germany
  • Hamburg, Germany, 20246
    • Local Institution - 0038
  • Tuebingen, Germany, 72076
    • Local Institution - 0039
  • Wuerzburg, Germany, 97080
    • Local Institution - 0037
• Italy
  • Milan, Italy, 20133
    • Local Institution - 0027
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0008
  • Sevilla, Spain, 41013
    • Local Institution - 0059
  • València, Spain, 46026
    • Local Institution - 0028
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28009
      • Local Institution - 0009
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Local Institution - 0029
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 0011

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A	Number of participants with dose-limiting toxicities (DLTs). DLTs were collected and evaluated for Part A within the DLT evaluation period, which started on Cycle 1 Day 1 (first dose) and ended at Day 42 (42 days after first dose of the study therapy).	From first dose to 42 days after first dose
Number of Participants With Adverse Events (AEs) - Part A	Number of participants with adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.	From first dose to 30 days after last dose (up to approximately 6 months)
Number of Participants With Serious Adverse Events (SAEs) - Part A	Number of participants with serious adverse events (SAEs). SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.	From first dose to 30 days after last dose (up to approximately 6 months)
Number of Participants With Drug-Related Adverse Events - Part A	Number of participants with drug-related adverse events. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.	From first dose to 30 days after last dose (up to approximately 6 months)
Number of Participants With Adverse Events Leading to Discontinuation - Part A	Number of participants with adverse events leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.	From first dose to 30 days after last dose (up to approximately 6 months)
Number of Participants Who Died - Part A	Number of participants who died.	From first dose to 30 days after last dose (up to approximately 6 months)
Maximum Observed Plasma Concentration (Cmax) - Part A	Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.	From first dose to 30 days after last dose (up to approximately 6 months)
Trough Observed Concentration (Ctrough) - Part A	Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.	From first dose to 30 days after last dose (up to approximately 6 months)
Area Under the Plasma Concentration (AUC) - Part A	Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.	From first dose to 30 days after last dose (up to approximately 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs	Part B	Up to 5 years
Incidence of SAEs	Part B	Up to 5 years
Incidence of drug-related AEs	Part B	Up to 5 years
Incidence of AEs leading to discontinuation	Part B	Up to 5 years
Incidence of death	Part B	Up to 5 years
Incidence of laboratory abnormalities: Hematology tests	Part B	Up to 5 years
Incidence of laboratory abnormalities: Clinical chemistry tests	Part B	Up to 5 years
Progression-free survival (PFS)	Part B	Up to 5 years
Overall survival (OS)	Part B	Up to 5 years

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Nektar Therapeutics

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2021
• Primary Completion (Actual): June 22, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; Immunotherapy; Ewing sarcoma; Melanoma; Medulloblastoma; Ependymoma; Rhabdomyosarcoma; IL-2; Neuroblastoma; Opdivo®; Pediatric cancer; Check point inhibitor; NKTR-214; B-cell leukemia/lymphoma/non-Hodgkin lymphoma (NHL); BEMPEG; Bempegaldesleukin; CD122-Biased Agonist; CD122-Biased Cytokine; High-grade glioma (HGG)/diffuse intrinsic pontine glioma (DIPG); IL-2 Receptor Agonist; Leukemia and lymphoma; Miscellaneous brain tumors; Miscellaneous solid tumors; NIVO; Non-rhabdomyosarcoma soft-tissue sarcomas; Pediatric malignancy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive; Neoplasms, Muscle Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Myosarcoma; Neoplasms; Sarcoma; Lymphoma; Leukemia; Glioma; Brain Neoplasms; Sarcoma, Ewing; Ependymoma; Medulloblastoma; Neuroblastoma; Rhabdomyosarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA045-020; 2020-000854-85 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No