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
• Interventions: Biological: Nivolumab; Biological: NKTR-214

• 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

Study Timeline

• Study First Submitted: 2021-01-26
• Study First Submitted QC: 2021-01-26
• Study First Posted: 2021-01-29
• Study Start: 2021-06-03
• Primary Completion: 2022-06-22
• Study Completion: 2022-06-22
• Results First Submitted: 2022-12-21
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-22
• Last Update Submitted: 2023-03-22
• Results First Posted: 2023-03-24
• Last Update Posted: 2023-03-24

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

Arm && Interventions

Group	Intervention	Description
A1F Dosing schema	NKTR-214	-
A2F Dosing schema	Nivolumab	-
Part B: Cohort B1 Neuroblastoma	NKTR-214	-
Part B: Cohort B2 Ewing sarcoma	Nivolumab	-
Part B: Cohort B9 Miscellaneous brain tumors	NKTR-214	-
A1W Dosing schema	Nivolumab	-
A1F Dosing schema	Nivolumab	-
Part B: Cohort B3 Rhabdomyosarcoma	Nivolumab	-
Part B: Cohort B5 NHL/leukemia	Nivolumab	-
Part B: Cohort B3 Rhabdomyosarcoma	NKTR-214	-
Part B: Cohort B4 Miscellaneous solid tumors	Nivolumab	-
Part B: Cohort B4 Miscellaneous solid tumors	NKTR-214	-
A2W Dosing schema	NKTR-214	-
A2F Dosing schema	NKTR-214	-
Part B: Cohort B5 NHL/leukemia	NKTR-214	-
Part B: Cohort B6 High-grade glioma	Nivolumab	-
Part B: Cohort B6 High-grade glioma	NKTR-214	-
Part B: Cohort B8 Ependymoma	NKTR-214	-
A1W Dosing schema	NKTR-214	-
A2W Dosing schema	Nivolumab	-
Part B: Cohort B1 Neuroblastoma	Nivolumab	-
Part B: Cohort B2 Ewing sarcoma	NKTR-214	-
Part B: Cohort B7 Medulloblastoma and Embryonal Tumors	Nivolumab	-
Part B: Cohort B7 Medulloblastoma and Embryonal Tumors	NKTR-214	-
Part B: Cohort B8 Ependymoma	Nivolumab	-
Part B: Cohort B9 Miscellaneous brain tumors	Nivolumab	-

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.

Trial Locations

Locations (18)

Local Institution - 0003; 🇦🇺 Perth, Western Australia, Australia

Local Institution - 0015; 🇫🇷 Paris, France

Local Institution - 0059; 🇪🇸 Sevilla, Spain

Local Institution; 🇦🇺 South Brisbane, Queensland, Australia

Local Institution - 0029; 🇺🇸 Little Rock, Arkansas, United States

Local Institution - 0016; 🇫🇷 Marseille, France

Local Institution - 0014; 🇫🇷 Lyon, France

Local Institution - 0038; 🇩🇪 Hamburg, Germany

Local Institution - 0008; 🇪🇸 Barcelona, Spain

Local Institution - 0001; 🇦🇺 Randwick, New South Wales, Australia

Local Institution - 0011; 🇺🇸 Saint Louis, Missouri, United States

Local Institution - 0039; 🇩🇪 Tuebingen, Germany

Local Institution - 0028; 🇪🇸 València, Spain

Local Institution - 0027; 🇮🇹 Milan, Italy

Local Institution - 0009; 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Local Institution - 0037; 🇩🇪 Wuerzburg, Germany

Local Institution - 0002; 🇦🇺 Parkville, Victoria, Australia

Local Institution - 0013; 🇫🇷 Villejuif, Val-de-Marne, France