Ependymoma, Ewing Sarcoma, High-grade Glioma, Leukemia and Lymphoma, Medulloblastoma, Miscellaneous Brain Tumors, Miscellaneous Solid Tumors, Neuroblastoma, Relapsed, Refractory Malignant Neoplasms, Rhabdomyosarcoma
Conditions
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
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.
Interventions
BIOLOGICALNivolumab
Specified dose on specified days
BIOLOGICALNKTR-214
Specified dose on specified days
Sponsors
Nektar Therapeutics
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, France, Germany, Italy, Spain, United States
Participant flow
Pre-assignment details
15 participants were treated in Part A. Study did not progress to Part B; therefore, no participants enrolled in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) Bempegaldesleukin 0.006 mg/kg + Nivolumab 4.5 mg/kg administered intravenously every 3 weeks | 8 |
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) Bempegaldesleukin 0.006 mg/kg + Nivolumab 360 mg administered intravenously every 3 weeks | 7 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression | 6 | 4 |
| Overall Study | Participant withdrew consent | 1 | 0 |
| Overall Study | Study drug toxicity | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) | Total | Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) |
|---|---|---|---|
| Age, Continuous | 14.9 Years STANDARD_DEVIATION 1.5 | 10.9 Years STANDARD_DEVIATION 4.8 | 7.5 Years STANDARD_DEVIATION 3.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 8 | 2 / 7 |
| other Total, other adverse events | 8 / 8 | 7 / 7 |
| serious Total, serious adverse events | 8 / 8 | 5 / 7 |
Outcome results
Primary
Area Under the Plasma Concentration (AUC) - Part A
Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: Data was not and will never be collected
Primary
Maximum Observed Plasma Concentration (Cmax) - Part A
Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: Data was not and will never be collected
Primary
Number of Participants Who Died - Part A
Number of participants who died.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: All treated participants in Part A
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) | Number of Participants Who Died - Part A | 2 Participants |
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) | Number of Participants Who Died - Part A | 0 Participants |
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.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: All treated participants in Part A
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) | Number of Participants With Adverse Events (AEs) - Part A | 8 Participants |
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) | Number of Participants With Adverse Events (AEs) - Part A | 7 Participants |
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.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: All treated participants in Part A
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) | Number of Participants With Adverse Events Leading to Discontinuation - Part A | 2 Participants |
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) | Number of Participants With Adverse Events Leading to Discontinuation - Part A | 3 Participants |
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).
Time frame: From first dose to 42 days after first dose
Population: All treated participants in Part A
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) | Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A | 0 Participants |
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) | Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A | 0 Participants |
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.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: All treated participants in Part A
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) | Number of Participants With Drug-Related Adverse Events - Part A | 6 Participants |
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) | Number of Participants With Drug-Related Adverse Events - Part A | 6 Participants |
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.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: All treated participants in Part A
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (4.5 mg/kg) | Number of Participants With Serious Adverse Events (SAEs) - Part A | 6 Participants |
| Part A: Bempegaldesleukin (0.006 mg/kg)+ Nivolumab (360 mg) | Number of Participants With Serious Adverse Events (SAEs) - Part A | 5 Participants |
Primary
Trough Observed Concentration (Ctrough) - Part A
Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
Time frame: From first dose to 30 days after last dose (up to approximately 6 months)
Population: Data was not and will never be collected