Clinical trial NCT04730349: A Study of Bempegaldesleukin (BEMPEG: NKTR-214) in Combination With Nivolumab in Children, Adolescents and Young Adults With Recurrent or Treatment-resistant Cancer
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Ependymoma
Ewing Sarcoma
High-grade Glioma
Leukemia and Lymphoma
Medulloblastoma
Miscellaneous Brain Tumors
Miscellaneous Solid Tumors
Neuroblastoma
Relapsed, Refractory Malignant Neoplasms
Rhabdomyosarcoma
Keywords: B-cell leukemia/lymphoma/non-Hodgkin lymphoma (NHL)
BEMPEG
Bempegaldesleukin
CD122-Biased Agonist
CD122-Biased Cytokine
Check point inhibitor
Ependymoma
Ewing sarcoma
High-grade glioma (HGG)/diffuse intrinsic pontine glioma (DIPG)
Immunotherapy
IL-2
IL-2 Receptor Agonist
Leukemia and lymphoma
Medulloblastoma
Melanoma
Miscellaneous brain tumors
Miscellaneous solid tumors
Neuroblastoma
Nivolumab
NKTR-214
NIVO
Non-rhabdomyosarcoma soft-tissue sarcomas
Opdivo®
Pediatric cancer
Pediatric malignancy
Rhabdomyosarcoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Nektar Therapeutics
First posted: 2021-01-29
Enrollment: 15
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A
timeFrame: From first dose to 42 days after first dose
measure: Number of Participants With Adverse Events (AEs) - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
measure: Number of Participants With Serious Adverse Events (SAEs) - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
measure: Number of Participants With Drug-Related Adverse Events - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
measure: Number of Participants With Adverse Events Leading to Discontinuation - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
measure: Number of Participants Who Died - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
measure: Maximum Observed Plasma Concentration (Cmax) - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
measure: Trough Observed Concentration (Ctrough) - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
measure: Area Under the Plasma Concentration (AUC) - Part A
timeFrame: From first dose to 30 days after last dose (up to approximately 6 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Local Institution - 0029
state: Arkansas
city: Saint Louis
country: United States
facility: Local Institution - 0011
state: Missouri
city: Randwick
country: Australia
facility: Local Institution - 0001
state: New South Wales
city: South Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Parkville
country: Australia
facility: Local Institution - 0002
state: Victoria
city: Perth
country: Australia
facility: Local Institution - 0003
state: Western Australia
city: Villejuif
country: France
facility: Local Institution - 0013
state: Val-de-Marne
city: Lyon
country: France
facility: Local Institution - 0014
city: Marseille
country: France
facility: Local Institution - 0016
city: Paris
country: France
facility: Local Institution - 0015
city: Hamburg
country: Germany
facility: Local Institution - 0038
city: Tuebingen
country: Germany
facility: Local Institution - 0039
city: Wuerzburg
country: Germany
facility: Local Institution - 0037
city: Milan
country: Italy
facility: Local Institution - 0027
city: Madrid
country: Spain
facility: Local Institution - 0009
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Local Institution - 0008
city: Sevilla
country: Spain
facility: Local Institution - 0059
city: València
country: Spain
facility: Local Institution - 0028
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: