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

Neuroblastoma Clinical Trial

— PIVOT IO 020  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04730349
• Other study ID #: CA045-020
• Secondary ID: 2020-000854-85
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 3, 2021
• Est. completion date: June 22, 2022

Study information

• Verified date: March 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: June 22, 2022
• Est. primary completion date: June 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 30 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• Nivolumab
Specified dose on specified days
• NKTR-214
Specified dose on specified days

Locations

Country	Name	City	State
Australia	Local Institution - 0002	Parkville	Victoria
Australia	Local Institution - 0003	Perth	Western Australia
Australia	Local Institution - 0001	Randwick	New South Wales
Australia	Local Institution	South Brisbane	Queensland
France	Local Institution - 0014	Lyon
France	Local Institution - 0016	Marseille
France	Local Institution - 0015	Paris
France	Local Institution - 0013	Villejuif	Val-de-Marne
Germany	Local Institution - 0038	Hamburg
Germany	Local Institution - 0039	Tuebingen
Germany	Local Institution - 0037	Wuerzburg
Italy	Local Institution - 0027	Milan
Spain	Local Institution - 0008	Barcelona
Spain	Local Institution - 0009	Madrid	Madrid, Comunidad De
Spain	Local Institution - 0059	Sevilla
Spain	Local Institution - 0028	València
United States	Local Institution - 0029	Little Rock	Arkansas
United States	Local Institution - 0011	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Nektar Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)

External Links

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