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

Phase 1

Terminated

Conditions: High-grade Glioma
Miscellaneous Brain Tumors
Miscellaneous Solid Tumors
Medulloblastoma
Ependymoma
Ewing Sarcoma
Leukemia and Lymphoma
Neuroblastoma
Relapsed, Refractory Malignant Neoplasms
Rhabdomyosarcoma

Registration Number: NCT04730349

Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 15

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 & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A	From first dose to 42 days after first dose	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).
Number of Participants With Adverse Events (AEs) - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	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.
Number of Participants With Serious Adverse Events (SAEs) - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	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.
Number of Participants With Drug-Related Adverse Events - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	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.
Number of Participants With Adverse Events Leading to Discontinuation - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	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.
Number of Participants Who Died - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	Number of participants who died.
Maximum Observed Plasma Concentration (Cmax) - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
Trough Observed Concentration (Ctrough) - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
Area Under the Plasma Concentration (AUC) - Part A	From first dose to 30 days after last dose (up to approximately 6 months)	Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (18): Local Institution - 0029
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Little Rock, Arkansas, United States
Local Institution - 0011
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Saint Louis, Missouri, United States
Local Institution - 0001
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Randwick, New South Wales, Australia
Local Institution
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South Brisbane, Queensland, Australia
Local Institution - 0002
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Parkville, Victoria, Australia
Local Institution - 0003
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Perth, Western Australia, Australia
Local Institution - 0013
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Villejuif, Val-de-Marne, France
Local Institution - 0014
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Lyon, France
Local Institution - 0016
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Marseille, France
Local Institution - 0015
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Paris, France
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Local Institution - 0029
🇺🇸Little Rock, Arkansas, United States